Is CFH p.Val941Phe (c.2821G>T) pathogenic?

CFH p.Val941Phe (c.2821G>T) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-09-17). AlphaMissense: likely benign (0.0834); Rare (popmax 0.358%, sas); Associated with complement factor H deficiency.

What condition is associated with CFH p.Val941Phe (c.2821G>T)?

CFH p.Val941Phe (c.2821G>T) is associated with complement factor H deficiency, basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFH p.Val941Phe (c.2821G>T) in the general population?

CFH p.Val941Phe (c.2821G>T) is rare (popmax 0.358%, sas) (gnomAD).

How is Immunodeficiency with factor H anomaly inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFH p.Val941Phe (c.2821G>T)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

CFH p.Val941Phe

c.2821G>T · rs529491401 · VCV1600648

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.358%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement factor H deficiency

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor loss, 38 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -1.7	GERP -3.3
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	0.192	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 0.358% South Asian · 326/91,062 alleles

Filtering AF 0.326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.313%

Overall 0.0217% 350/1,613,712 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.358%	279
Remaining individualsnot grpmax-eligible	0.032%	3,125
Middle Eastern	0.0165%	6,058
African / African-American	0.00133%	74,920
European (non-Finnish)	0.00017%	589,950

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.Val941Phe
Coding: c.2821G>T
MANE Select: NM_000186
dbSNP: rs529491401
Type: single nucleotide variant
Location: chr1:196740657 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 941: the sushi 16 domain; a β-strand; a disulfide bond

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

Disease context

complement factor H deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: basal laminar drusen hemolytic uremic syndrome, atypical, susceptibility to, 1 age related macular degeneration 4 atypical hemolytic-uremic syndrome

For Immunodeficiency with factor H anomaly (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive

Similar variants

CFH p.Val941Ala 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-val941phe (accessed [today's date]).

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