Is CFH p.Ser890Ile (c.2669G>T) pathogenic?

CFH p.Ser890Ile (c.2669G>T) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-09-17). AlphaMissense: likely benign (0.0949); Common (popmax 20.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with age related macular degeneration 4.

What condition is associated with CFH p.Ser890Ile (c.2669G>T)?

CFH p.Ser890Ile (c.2669G>T) is associated with age related macular degeneration 4, basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

What do computational predictors say about CFH p.Ser890Ile (c.2669G>T)?

AlphaMissense predicts likely benign (score 0.0949) — an in-silico prediction, not a clinical call.

CFH p.Ser890Ile

Q: How common is CFH p.Ser890Ile (c.2669G>T) in the general population?

CFH p.Ser890Ile (c.2669G>T) is common (popmax 20.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2669G>T · rs515299 · VCV294507

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0949 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 20.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

age related macular degeneration 4

Computational evidence

Protein change
AlphaMissense	0.0949	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -3.7
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	0.081	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.1% African / African-American · 15,025/74,924 alleles

Filtering AF 19.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.7%

Overall 1.19% 19,201/1,613,318 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20.1%	5
Ashkenazi Jewishnot grpmax-eligible	2.88%	35
Remaining individualsnot grpmax-eligible	1.85%	54
Middle Eastern	1.67%	60
Admixed American	1.57%	64
South Asian	0.157%	637
European (non-Finnish)	0.0833%	1,200

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CFH
Protein: p.Ser890Ile
Coding: c.2669G>T
MANE Select: NM_000186
dbSNP: rs515299
Type: single nucleotide variant
Location: chr1:196737547 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 890: the sushi 15 domain; a β-strand; a disulfide bond; a UniProt-annotated variant site (in)

Full CFH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: basal laminar drusen hemolytic uremic syndrome, atypical, susceptibility to, 1 complement factor H deficiency atypical hemolytic-uremic syndrome

Similar variants

CFH p.Ser890Thr Uncertain significance ★ ⚠ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.350+1G>T Pathogenic/Likely pathogenic ★★ same condition
CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg1215Leu Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cfh-p-ser890ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown