Is FERMT1 p.Ala232Glu (c.695C>A) pathogenic?

FERMT1 p.Ala232Glu (c.695C>A) is classified Benign in FERMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-27). AlphaMissense: likely benign (0.1808); Rare (popmax 0.238%, sas).

How common is FERMT1 p.Ala232Glu (c.695C>A) in the general population?

FERMT1 p.Ala232Glu (c.695C>A) is rare (popmax 0.238%, sas) (gnomAD).

What do computational predictors say about FERMT1 p.Ala232Glu (c.695C>A)?

AlphaMissense predicts likely benign (score 0.1808) — an in-silico prediction, not a clinical call.

FERMT1 p.Ala232Glu

c.695C>A · rs147864238 · VCV2182782

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1808 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.238%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1808	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 0.27, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 3.8e-05 · regional, not allelic
Overall
CADD	22.3	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 0.238% South Asian · 217/91,060 alleles

Filtering AF 0.212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.202%

Overall 0.0139% 225/1,613,728 alleles · rare exomes 215/1,461,466 · genomes 10/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.238%	420
Middle Eastern	0.017%	5,880
Remaining individualsnot grpmax-eligible	0.0096%	10,413
European (non-Finnish)	8.48e-05%	1,179,889

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: FERMT1
Protein: p.Ala232Glu
Coding: c.695C>A
MANE Select: NM_017671
dbSNP: rs147864238
Type: single nucleotide variant
Location: chr20:6110349 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 232: the ferm domain

Full FERMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FERMT1 p.Ala232Val Uncertain significance ★★ ⚠ same residue
FERMT1 c.1371+4A>G Pathogenic ★★ same type
FERMT1 c.532+1G>A Likely pathogenic ★★ same type
FERMT1 p.Arg110Ter Pathogenic ★★ same type
FERMT1 p.Arg271Ter Pathogenic ★★ same type
FERMT1 p.Arg288Ter Pathogenic ★★ same type
FERMT1 p.Glu304Ter Pathogenic ★★ same type
FERMT1 p.Trp298Ter Pathogenic ★★ same type

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/fermt1-p-ala232glu (accessed [today's date]).

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