CFH (Complement factor H) variants and mutations
CFH (also known as Complement factor H) is a human protein-coding gene encoding a complement factor H protein. It restrains the alternative complement pathway on host surfaces and in plasma, protecting tissues from uncontrolled complement amplification. Pathogenic variants or risk alleles are associated with atypical hemolytic uremic syndrome, C3 glomerulopathy, and age-related macular degeneration. This analysis covers 262 CFH variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes complement factor H deficiency, age-related macular degeneration, and atypical hemolytic-uremic syndrome. Example CFH variants include R2T, R2K, and R2R.
Variant analysis overview
- Gene: CFH
- Protein: Complement factor H
- UniProt accession: P08603
- Organism: Homo sapiens
- Variants analyzed: 262
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 56 unspecified-consequence records; 1 natural variant; 138 missense variants; 51 synonymous variants; 5 frameshift variants; 4 stop-gained variants; 1 splice-region variants; 1 splice acceptor variant; 2 in-frame deletions; 1 substitution
- Prediction scores: 256 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: complement factor H deficiency, age-related macular degeneration, atypical hemolytic-uremic syndrome, age related macular degeneration 4, Familial drusen, retinal disorder, degeneration of macula and posterior pole, macular degeneration, dense deposit disease, wet macular degeneration, atypical hemolytic-uremic syndrome with H factor anomaly, dry age related macular degeneration.
Protein structure and variant hotspots
- Protein features: 20 domains; 9 post-translational modification sites.
- Structural context: 219 variants have structural context.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable CFH variants
Examples include R2T, R2K, R2R, L3I, L3F, L3V, L4P, L4L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- R2T (p.Arg2Thr), rs142266551, gnomAD 1-196652122-G-C, REVEL 0.15, CADD 16.90
- R2K (p.Arg2Lys), gnomAD 1-196652122-G-A, REVEL 0.09, CADD 11.40
- R2R (p.Arg2Arg), rs1370352396, gnomAD 1-196652123-A-G, CADD 8.13
- L3I (p.Leu3Ile), gnomAD 1-196652124-C-A, REVEL 0.45, CADD 15.40
- L3F (p.Leu3Phe), rs139254423, gnomAD 1-196652124-C-T, REVEL 0.04, CADD 4.89
- L3V (p.Leu3Val), rs139254423, gnomAD 1-196652124-C-G, REVEL 0.63, CADD 11.50
- L4P (p.Leu4Pro), rs1305521799, gnomAD 1-196652128-T-C, REVEL 0.03, CADD 5.10
- L4L (p.Leu4Leu), rs905194672, gnomAD 1-196652129-A-G, CADD 4.45
- K6E (p.Lys6Glu), rs749875053, gnomAD 1-196652133-A-G, REVEL 0.07, CADD 11.10
- K6R (p.Lys6Arg), rs1356316928, gnomAD 1-196652134-A-G, REVEL 0.03, CADD 7.75
- K6N (p.Lys6Asn), gnomAD 1-196652135-G-C, REVEL 0.09, CADD 15.00
- I7F (p.Ile7Phe), gnomAD 1-196652136-A-T, REVEL 0.01, CADD 18.50
- I7I (p.Ile7Ile), rs766324414, gnomAD 1-196652138-T-C, CADD 8.54
- I8L (p.Ile8Leu), rs1447569980, gnomAD 1-196652139-A-C, REVEL 0.05, CADD 9.59
- C9R (p.Cys9Arg), gnomAD 1-196652142-T-C, REVEL 0.16, CADD 22.70
- C9W (p.Cys9Trp), rs755765120, gnomAD 1-196652144-C-G, REVEL 0.04, CADD 13.60
- L10F (p.Leu10Phe), rs1375316866, gnomAD 1-196652145-C-T, REVEL 0.04, CADD 16.00
- L10P (p.Leu10Pro), gnomAD 1-196652146-T-C, REVEL 0.27, CADD 25.50
- L10L (p.Leu10Leu), gnomAD 1-196652147-T-C, CADD 7.53
- M11T (p.Met11Thr), rs1666520560, gnomAD 1-196652149-T-C, REVEL 0.07, CADD 9.51
- M11I (p.Met11Ile), gnomAD 1-196652150-G-A, REVEL 0.01, CADD 0.01
- L12S (p.Leu12Ser), gnomAD 1-196652152-T-C, REVEL 0.11, CADD 23.20
- W13G (p.Trp13Gly), rs1200969813, gnomAD 1-196652154-T-G, REVEL 0.23, CADD 26.60
- W13R (p.Trp13Arg), gnomAD 1-196652154-T-C, REVEL 0.26, CADD 25.10
- A14P (p.Ala14Pro), rs1285086946, gnomAD 1-196652157-G-C, REVEL 0.12, CADD 18.00
- A14V (p.Ala14Val), rs749713710, gnomAD 1-196652158-C-T, REVEL 0.07, CADD 20.40
- A14A (p.Ala14Ala), rs1666521255, gnomAD 1-196652159-T-C, CADD 10.50
- I15V (p.Ile15Val), rs1391516616, gnomAD 1-196652160-A-G, REVEL 0.03, CADD 9.38
- I15T (p.Ile15Thr), rs768874309, gnomAD 1-196652161-T-C, REVEL 0.05, CADD 22.50
- C16L (p.Cys16Leu), rs1354648948, gnomAD 1-196652163-TG-T, CADD 32.00
- C16S (p.Cys16Ser), gnomAD 1-196652164-G-C, REVEL 0.27, CADD 27.10
- C16Y (p.Cys16Tyr), gnomAD 1-196652164-G-A, REVEL 0.44, CADD 28.00
- V17I (p.Val17Ile), gnomAD 1-196652166-G-A, REVEL 0.02, CADD 14.30
- V17E (p.Val17Glu), gnomAD 1-196652167-T-A, REVEL 0.15, CADD 23.40
- A18S (p.Ala18Ser), rs779300578, gnomAD 1-196652169-G-T, REVEL 0.11, CADD 24.00
- A18T (p.Ala18Thr), gnomAD 1-196652169-G-A, REVEL 0.09, CADD 26.40
- A18E (p.Ala18Glu), gnomAD 1-196652170-C-A, REVEL 0.18, CADD 22.60
- A18G (p.Ala18Gly), gnomAD 1-196652170-C-G, REVEL 0.11, CADD 22.60
- A18A (p.Ala18Ala), gnomAD 1-196652171-A-C, CADD 12.90
- E19K (p.Glu19Lys), rs748624911, gnomAD 1-196652172-G-A, REVEL 0.13, CADD 8.62
- E19D (p.Glu19Asp), gnomAD 1-196652174-A-T, REVEL 0.14, CADD 27.60
- D20G (p.Asp20Gly), gnomAD 1-196672978-A-G, REVEL 0.26, CADD 23.90
- C21S (p.Cys21Ser), gnomAD 1-196672981-G-C, REVEL 0.68, CADD 23.80
- N22D (p.Asn22Asp), rs761662067, gnomAD 1-196672983-A-G, REVEL 0.07, CADD 6.98
- N22S (p.Asn22Ser), rs767494411, gnomAD 1-196672984-A-G, REVEL 0.05, CADD 8.99
- N22K (p.Asn22Lys), gnomAD 1-196672985-T-A, REVEL 0.03, CADD 0.00
- E23K (p.Glu23Lys), rs754932801, gnomAD 1-196672986-G-A, REVEL 0.06, CADD 21.80
- E23G (p.Glu23Gly), rs773104581, gnomAD 1-196672987-A-G, REVEL 0.02, CADD 4.92
- E23E (p.Glu23Glu), rs1558154228, gnomAD 1-196672988-A-G, CADD 3.69
- L24V (p.Leu24Val), rs928296341, gnomAD 1-196672989-C-G, REVEL 0.10, CADD 16.60
- L24F (p.Leu24Phe), rs928296341, gnomAD 1-196672989-C-T, REVEL 0.14, CADD 19.00
- L24H (p.Leu24His), rs1007759235, gnomAD 1-196672990-T-A, REVEL 0.10, CADD 22.70
- L24P (p.Leu24Pro), rs1007759235, gnomAD 1-196672990-T-C, REVEL 0.06, CADD 13.70
- L24L (p.Leu24Leu), rs1667334953, gnomAD 1-196672991-T-A, CADD 1.92
- P25S (p.Pro25Ser), gnomAD 1-196672992-C-T, REVEL 0.31, CADD 23.50
- P25P (p.Pro25Pro), rs1558154243, gnomAD 1-196672994-T-G, CADD 6.61
- P26S (p.Pro26Ser), rs866627729, gnomAD 1-196672995-C-T, REVEL 0.34, CADD 23.10
- P26L (p.Pro26Leu), gnomAD 1-196672996-C-T, REVEL 0.39, CADD 24.40
- P26P (p.Pro26Pro), rs760566051, gnomAD 1-196672997-A-G, CADD 6.30
- R27G (p.Arg27Gly), rs1381537563, gnomAD 1-196672998-A-G, REVEL 0.16, CADD 23.40
- R27T (p.Arg27Thr), rs1166473674, gnomAD 1-196672999-G-C, REVEL 0.11, CADD 7.42
- R27K (p.Arg27Lys), gnomAD 1-196672999-G-A, REVEL 0.09, CADD 0.86
- R28I (p.Arg28Ile), rs796052137, gnomAD 1-196672999-GAAGA, CADD 19.70
- N29H (p.Asn29His), gnomAD 1-196673004-A-C, REVEL 0.27, CADD 7.68
- N29K (p.Asn29Lys), gnomAD 1-196673006-T-A, REVEL 0.11, CADD 10.30
- T30S (p.Thr30Ser), gnomAD 1-196673007-A-T, REVEL 0.03, CADD 1.08
- T30T (p.Thr30Thr), gnomAD 1-196673009-A-C, CADD 6.33
- I32N (p.Ile32Asn), gnomAD 1-196673014-T-A, REVEL 0.45, CADD 24.90
- L33L (p.Leu33Leu), rs1198670538, gnomAD 1-196673018-G-A, CADD 0.95
- T34S (p.Thr34Ser), rs1389897706, gnomAD 1-196673019-A-T, REVEL 0.07, CADD 0.25
- T34I (p.Thr34Ile), rs765897045, gnomAD 1-196673020-C-T, REVEL 0.26, CADD 17.50
- T34R (p.Thr34Arg), rs765897045, gnomAD 1-196673020-C-G, REVEL 0.62, CADD 14.20
- T34K (p.Thr34Lys), rs765897045, gnomAD 1-196673020-C-A, REVEL 0.18, CADD 17.50
- T34T (p.Thr34Thr), rs1667335883, gnomAD 1-196673021-A-T, CADD 1.44
- G35R (p.Gly35Arg), rs886045742, gnomAD 1-196673022-G-C, REVEL 0.56, CADD 24.60
- G35G (p.Gly35Gly), gnomAD 1-196673024-T-A, CADD 3.75
- S36F (p.Ser36Phe), rs1424121446, gnomAD 1-196673026-C-T, REVEL 0.27, CADD 22.60
- S36Y (p.Ser36Tyr), gnomAD 1-196673026-C-A, REVEL 0.28, CADD 22.10
- S36S (p.Ser36Ser), rs781060260, gnomAD 1-196673027-C-T, CADD 3.63
- W37R (p.Trp37Arg), gnomAD 1-196673028-T-C, REVEL 0.35, CADD 23.00
- W37S (p.Trp37Ser), gnomAD 1-196673029-G-C, REVEL 0.30, CADD 25.00
- W37C (p.Trp37Cys), gnomAD 1-196673030-G-T, REVEL 0.35, CADD 25.40
- S38C (p.Ser38Cys), gnomAD 1-196673032-C-G, REVEL 0.06, CADD 6.17
- S38S (p.Ser38Ser), gnomAD 1-196673033-T-C, CADD 4.04
- D39H (p.Asp39His), gnomAD 1-196673034-G-C, REVEL 0.17, CADD 22.70
- D39N (p.Asp39Asn), rs1180008280, gnomAD 1-196673034-G-A, REVEL 0.12, CADD 19.90
- D39Y (p.Asp39Tyr), gnomAD 1-196673034-G-T, REVEL 0.20, CADD 22.90
- D39D (p.Asp39Asp), gnomAD 1-196673036-C-T, CADD 0.12
- Q40* (p.Gln40Ter), gnomAD 1-196673037-C-T, CADD 23.20
- T41I (p.Thr41Ile), rs1192717326, gnomAD 1-196673041-C-T, REVEL 0.10, CADD 11.80
- T41T (p.Thr41Thr), rs1261273441, gnomAD 1-196673042-A-G, CADD 0.77
- Y42S (p.Tyr42Ser), gnomAD 1-196673041-CAT-C, CADD 22.50
- Y42D (p.Tyr42Asp), gnomAD 1-196673043-T-G, REVEL 0.49, CADD 23.30
- Y42F (p.Tyr42Phe), rs182750499, gnomAD 1-196673044-A-T, REVEL 0.36, CADD 22.00
- Y42Y (p.Tyr42Tyr), gnomAD 1-196673045-T-C, CADD 1.14
- P43A (p.Pro43Ala), rs764941928, gnomAD 1-196673046-C-G, REVEL 0.04, CADD 6.66
- P43T (p.Pro43Thr), rs764941928, gnomAD 1-196673046-C-A, REVEL 0.08, CADD 13.80
- G45S (p.Gly45Ser), gnomAD 1-196673052-G-A, REVEL 0.49, CADD 22.60
- G45D (p.Gly45Asp), rs758810701, gnomAD 1-196673053-G-A, REVEL 0.52, CADD 22.60
- G45G (p.Gly45Gly), gnomAD 1-196673054-C-T, CADD 6.83
- T46A (p.Thr46Ala), rs778461886, gnomAD 1-196673055-A-G, REVEL 0.34, CADD 23.00
- T46T (p.Thr46Thr), gnomAD 1-196673057-C-G, CADD 0.09
- A48V (p.Ala48Val), rs1160820929, gnomAD 1-196673062-C-T, REVEL 0.17, CADD 21.30
- A48A (p.Ala48Ala), gnomAD 1-196673063-T-A, CADD 0.40
- I49V (p.Ile49Val), rs747546121, gnomAD 1-196673064-A-G, REVEL 0.01, CADD 0.00
- K51T (p.Lys51Thr), gnomAD 1-196673071-A-C, REVEL 0.42, CADD 23.20
- K51K (p.Lys51Lys), gnomAD 1-196673072-A-G, CADD 7.42
- C52Y (p.Cys52Tyr), rs1419451167, gnomAD 1-196673074-G-A, REVEL 0.94, CADD 24.30
- R53C (p.Arg53Cys), rs757785149, gnomAD 1-196673076-C-T, REVEL 0.50, CADD 23.80
- R53S (p.Arg53Ser), gnomAD 1-196673076-C-A, REVEL 0.44, CADD 23.00
- R53L (p.Arg53Leu), rs976333015, gnomAD 1-196673077-G-T, REVEL 0.40, CADD 23.30
- R53H (p.Arg53His), rs976333015, gnomAD 1-196673077-G-A, REVEL 0.39, CADD 22.50
- R53R (p.Arg53Arg), gnomAD 1-196673078-C-A, CADD 2.33
- P54R (p.Pro54Arg), gnomAD 1-196673080-C-G, REVEL 0.41, CADD 23.70
- P54P (p.Pro54Pro), gnomAD 1-196673081-T-C, CADD 7.40
- G55R (p.Gly55Arg), rs1667337715, gnomAD 1-196673082-G-A, REVEL 0.76, CADD 24.90
- G55G (p.Gly55Gly), gnomAD 1-196673084-A-G, CADD 1.87
- Y56Y (p.Tyr56Tyr), rs1667337834, gnomAD 1-196673087-T-C, CADD 3.31
- R57I (p.Arg57Ile), gnomAD 1-196673089-G-T, REVEL 0.29, CADD 17.80
- R57R (p.Arg57Arg), gnomAD 1-196673090-A-G, CADD 7.21
- S58A (p.Ser58Ala), rs141336681, gnomAD 1-196673091-T-G, REVEL 0.10, CADD 19.00
- S58S (p.Ser58Ser), rs1667338008, gnomAD 1-196673093-T-C, CADD 0.83
- L59L (p.Leu59Leu), gnomAD 1-196673096-T-G, CADD 0.76
- N61D (p.Asn61Asp), rs769975480, gnomAD 1-196673100-A-G, REVEL 0.14, CADD 13.80
- N61S (p.Asn61Ser), gnomAD 1-196673101-A-G, REVEL 0.06, CADD 0.67
- N61N (p.Asn61Asn), rs1230917528, gnomAD 1-196673102-T-C, CADD 2.07
- V62I (p.Val62Ile), rs800292, UniProt VAR 023836, REVEL 0.14, CADD 7.64, Benign/Likely benign, Atypical hemolytic-uremic syndrome; Factor H deficiency; Age related macular deg
- V62L (p.Val62Leu), gnomAD 1-196673103-G-C, REVEL 0.12, CADD 17.60
- I63T (p.Ile63Thr), gnomAD 1-196673107-T-C, REVEL 0.04, CADD 4.26
- V65I (p.Val65Ile), rs747978546, gnomAD 1-196673112-G-A, REVEL 0.06, CADD 0.16
- V65G (p.Val65Gly), gnomAD 1-196673113-T-G, REVEL 0.20, CADD 6.01
- V65A (p.Val65Ala), gnomAD 1-196673113-T-C, REVEL 0.08, CADD 0.02
- V65V (p.Val65Val), rs771886580, gnomAD 1-196673114-A-G, CADD 1.18
- R67R (p.Arg67Arg), rs1667339143, gnomAD 1-196673118-A-C, CADD 7.27
- R67T (p.Arg67Thr), gnomAD 1-196673119-G-C, REVEL 0.17, CADD 0.03
- R67M (p.Arg67Met), gnomAD 1-196673119-G-T, REVEL 0.24, CADD 1.76
- K68Q (p.Lys68Gln), rs1667339290, gnomAD 1-196673121-A-C, REVEL 0.04, CADD 3.75
- K68N (p.Lys68Asn), gnomAD 1-196673123-G-T, REVEL 0.09, CADD 0.00
- G69R (p.Gly69Arg), rs760619101, gnomAD 1-196673124-G-C, REVEL 0.42, CADD 24.20
- W71* (p.Trp71Ter), rs1210674261, gnomAD 1-196673132-G-A, CADD 36.00
- V72L (p.Val72Leu), rs766241195, gnomAD 1-196673133-G-C, REVEL 0.07, CADD 17.40
- V72I (p.Val72Ile), rs766241195, gnomAD 1-196673133-G-A, REVEL 0.14, CADD 16.80
- V72F (p.Val72Phe), rs766241195, gnomAD 1-196673133-G-T, REVEL 0.34, CADD 22.10
- V72V (p.Val72Val), gnomAD 1-196673135-T-C, CADD 0.84
- A73P (p.Ala73Pro), gnomAD 1-196673136-G-C, REVEL 0.23, CADD 1.51
- A73V (p.Ala73Val), rs1431540496, gnomAD 1-196673137-C-T, REVEL 0.24, CADD 22.70
- A73A (p.Ala73Ala), rs776075595, gnomAD 1-196673138-T-C, CADD 3.66
- L74F (p.Leu74Phe), rs368835171, gnomAD 1-196673139-C-T, REVEL 0.16, CADD 15.60
- L74R (p.Leu74Arg), gnomAD 1-196673140-T-G, REVEL 0.26, CADD 20.40
- N75H (p.Asn75His), rs1439683865, gnomAD 1-196673142-A-C, REVEL 0.05, CADD 2.14
- N75T (p.Asn75Thr), gnomAD 1-196673143-A-C, REVEL 0.30, CADD 19.00
- N75K (p.Asn75Lys), rs764849497, gnomAD 1-196673144-T-A, REVEL 0.29, CADD 14.50
- L77S (p.Leu77Ser), rs752361141, gnomAD 1-196673149-T-C, REVEL 0.01, CADD 0.36
- R78G (p.Arg78Gly), UniProt VAR 025864, REVEL 0.32, CADD 22.60, Conflicting interpretations, Factor H deficiency; Atypical hemolytic-uremic syndrome; Hemolytic uremic syndro
- R78T (p.Arg78Thr), rs758081247, gnomAD 1-196673152-G-C, REVEL 0.19, CADD 7.85
- K79R (p.Lys79Arg), rs1247978300, gnomAD 1-196673155-A-G, REVEL 0.03, CADD 1.77
- K79K (p.Lys79Lys), rs1313344842, gnomAD 1-196673156-A-G, CADD 1.79
- C80Y (p.Cys80Tyr), rs764571169, gnomAD 1-196673158-G-A, REVEL 0.92, CADD 25.00
- C80C (p.Cys80Cys), rs1667341617, gnomAD 1-196673159-T-C, CADD 7.99
- Q81H (p.Gln81His), gnomAD 1-196673162-G-C, REVEL 0.03, CADD 11.40
- Q81Q (p.Gln81Gln), gnomAD 1-196673162-G-A, CADD 6.55
- K82S (p.Lys82Ser), gnomAD 1-196673854-TAGAA, CADD 35.00
- K82R (p.Lys82Arg), rs376337060, gnomAD 1-196673857-A-G, REVEL 0.00, CADD 23.00
- K82I (p.Lys82Ile), gnomAD 1-196673857-A-T, REVEL 0.23, CADD 30.00
- R83M (p.Arg83Met), rs942264542, gnomAD 1-196673860-G-T, REVEL 0.22, CADD 16.50
- R83R (p.Arg83Arg), rs1258731941, gnomAD 1-196673861-G-A, CADD 6.19
- R83S (p.Arg83Ser), gnomAD 1-196673861-G-T, REVEL 0.64, CADD 15.50
- P84T (p.Pro84Thr), rs1457877597, gnomAD 1-196673862-C-A, REVEL 0.18, CADD 24.20
- P84P (p.Pro84Pro), rs1215359473, gnomAD 1-196673864-C-T, CADD 8.07
- C85F (p.Cys85Phe), gnomAD 1-196673866-G-T, REVEL 0.97, CADD 27.60
- C85Y (p.Cys85Tyr), gnomAD 1-196673866-G-A, REVEL 0.97, CADD 27.00
- G86* (p.Gly86Ter), rs1667368443, gnomAD 1-196673868-G-T, CADD 40.00
- G86E (p.Gly86Glu), rs1317403430, gnomAD 1-196673869-G-A, REVEL 0.38, MetaLR 0.35
- H87N (p.His87Asn), gnomAD 1-196673871-C-A, REVEL 0.16, MetaLR 0.23
- G89E (p.Gly89Glu), gnomAD 1-196673876-TG-T, CADD 32.00
- G89* (p.Gly89Ter), gnomAD 1-196673877-G-T, CADD 41.00
- G89G (p.Gly89Gly), rs1197262936, gnomAD 1-196673879-A-G, CADD 12.10, SIFT 0.00
- D90G (p.Asp90Gly), rs1239695899, gnomAD 1-196673881-A-G, REVEL 0.76, MetaLR 0.46
- D90D (p.Asp90Asp), gnomAD 1-196673882-T-C, CADD 1.54, SIFT 1.00
- T91S (p.Thr91Ser), rs771527214, gnomAD 1-196673884-C-G, REVEL 0.23, MetaLR 0.25
Public CFH analysis runs
- CFH analysis run — CFH (262 variants) — completed 2026-08-19