Is FERMT1 p.Ala232Val (c.695C>T) pathogenic?

FERMT1 p.Ala232Val (c.695C>T) is classified Uncertain significance in FERMT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-01). AlphaMissense: likely benign (0.0873); Ultra-rare (popmax 0.0224%, nfe); Associated with Kindler syndrome.

What condition is associated with FERMT1 p.Ala232Val (c.695C>T)?

FERMT1 p.Ala232Val (c.695C>T) is associated with Kindler syndrome (ClinVar).

How common is FERMT1 p.Ala232Val (c.695C>T) in the general population?

FERMT1 p.Ala232Val (c.695C>T) is ultra-rare (popmax 0.0224%, nfe) (gnomAD).

How is Kindler epidermolysis bullosa inherited?

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

What do computational predictors say about FERMT1 p.Ala232Val (c.695C>T)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

FERMT1 p.Ala232Val

c.695C>T · rs147864238 · VCV339227

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0224%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Kindler syndrome

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -4.59	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 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	21.1	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 0.0224% European (non-Finnish) · 264/1,179,890 alleles

Filtering AF 0.0201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0193%

Overall 0.0183% 295/1,613,728 alleles · ultra-rare exomes 272/1,461,466 · genomes 23/152,262 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0224%	4,469
South Asian	0.0121%	8,278
Admixed American	0.0117%	8,572
Remaining individualsnot grpmax-eligible	0.008%	12,496
Finnishnot grpmax-eligible	0.00625%	16,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
African / African-American	0.00267%	37,506
East Asian	0.00223%	44,876

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.Ala232Val
Coding: c.695C>T
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

Disease context

Kindler syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Kindler epidermolysis bullosa (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

FERMT1 p.Ala232Glu Benign ★ same residue
FERMT1 c.1371+4A>G Pathogenic ★★ same condition
FERMT1 p.Arg110Ter Pathogenic ★★ same condition
FERMT1 p.Arg271Ter Pathogenic ★★ same condition
FERMT1 p.Arg288Ter Pathogenic ★★ same condition
FERMT1 p.Glu304Ter Pathogenic ★★ same condition
FERMT1 c.*1004G>A Uncertain significance ★★ same condition
FERMT1 c.*1076C>T Uncertain significance ★★ 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/fermt1-p-ala232val (accessed [today's date]).

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