Is CFH p.Val111Glu (c.332T>A) pathogenic?

CFH p.Val111Glu (c.332T>A) is classified Uncertain significance in CFH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.2014); Ultra-rare (popmax 0.0714%, sas); Associated with basal laminar drusen.

What condition is associated with CFH p.Val111Glu (c.332T>A)?

CFH p.Val111Glu (c.332T>A) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, complement factor H deficiency (ClinVar).

How common is CFH p.Val111Glu (c.332T>A) in the general population?

CFH p.Val111Glu (c.332T>A) is ultra-rare (popmax 0.0714%, sas) (gnomAD).

What do computational predictors say about CFH p.Val111Glu (c.332T>A)?

AlphaMissense predicts likely benign (score 0.2014) — an in-silico prediction, not a clinical call.

CFH p.Val111Glu

c.332T>A · rs576819823 · VCV1403151

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2014 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0714%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

basal laminar drusen

Computational evidence

Protein change
AlphaMissense	0.2014	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -7.02	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.84 · regional, not allelic
Overall
CADD	24.7	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 0.0714% South Asian · 65/91,032 alleles

Filtering AF 0.0574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00447% 72/1,611,440 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0714%	1,400
Remaining individualsnot grpmax-eligible	0.00961%	10,402
European (non-Finnish)	8.49e-05%	1,177,711

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.Val111Glu
Coding: c.332T>A
MANE Select: NM_000186
dbSNP: rs576819823
Type: single nucleotide variant
Location: chr1:196673944 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 111: a β-strand; the sushi 2 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 atypical hemolytic-uremic syndrome

Similar variants

CFH p.Val111Leu Uncertain significance ★★ ⚠ same residue
CFH p.Val111= Likely benign ★ 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

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-val111glu (accessed [today's date]).

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