Is CFH p.Pro923Ser (c.2767C>T) pathogenic?

CFH p.Pro923Ser (c.2767C>T) is classified Uncertain significance in CFH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-20). AlphaMissense: likely benign (0.1108); Very rare (popmax 0.00935%, afr); Associated with basal laminar drusen.

What condition is associated with CFH p.Pro923Ser (c.2767C>T)?

CFH p.Pro923Ser (c.2767C>T) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, complement factor H deficiency (ClinVar).

How common is CFH p.Pro923Ser (c.2767C>T) in the general population?

CFH p.Pro923Ser (c.2767C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about CFH p.Pro923Ser (c.2767C>T)?

AlphaMissense predicts likely benign (score 0.1108) — an in-silico prediction, not a clinical call.

CFH p.Pro923Ser

c.2767C>T · rs368846503 · VCV1444110

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

basal laminar drusen

Computational evidence

Protein change
AlphaMissense	0.1108	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -6.67	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 -2	GERP -0.16
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	17.26	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,876 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,613,126 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,697
European (non-Finnish)	8.48e-05%	1,179,473

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.Pro923Ser
Coding: c.2767C>T
MANE Select: NM_000186
dbSNP: rs368846503
Type: single nucleotide variant
Location: chr1:196737645 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 923: the sushi 15 domain; a disulfide bond

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

Disease context

basal laminar drusen — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hemolytic uremic syndrome, atypical, susceptibility to, 1 complement factor H deficiency age related macular degeneration 4

Similar variants

CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.2236+1G>C 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.Arg1215Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg232Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg53Cys Pathogenic/Likely pathogenic ★★ same condition
CFH p.Cys431Ser 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-pro923ser (accessed [today's date]).

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