Is KRT85 p.Val232Met (c.694G>A) pathogenic?

KRT85 p.Val232Met (c.694G>A) is classified Uncertain significance in KRT85 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: ambiguous (0.3847); Very rare (popmax 0.00329%, sas).

How common is KRT85 p.Val232Met (c.694G>A) in the general population?

KRT85 p.Val232Met (c.694G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about KRT85 p.Val232Met (c.694G>A)?

AlphaMissense predicts ambiguous (score 0.3847) — an in-silico prediction, not a clinical call.

KRT85 p.Val232Met

c.694G>A · rs764225566 · VCV2303650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
AlphaMissense	0.3847	ambiguous
REVEL	0.553	indeterminate
SaProt	LLR -10.28	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,136 bp · p 0.65 · regional, not allelic
Overall
CADD	24.8	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 0.00329% South Asian · 3/91,090 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00112% 18/1,614,024 alleles · very rare exomes 16/1,461,822 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00119%	84,285

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: KRT85
Protein: p.Val232Met
Coding: c.694G>A
MANE Select: NM_002283
dbSNP: rs764225566
Type: single nucleotide variant
Location: chr12:52364160 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.09
Residue 232: the if rod domain; the 'coil 1b' region

Full KRT85 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT85 p.Arg142His Uncertain significance ★★ ⚠ same type
KRT85 p.Arg315His Uncertain significance ★★ ⚠ same type
KRT85 p.Arg465His Uncertain significance ★★ ⚠ same type
KRT85 p.Asn115Lys Uncertain significance ★★ ⚠ same type
KRT85 p.Glu352Lys Uncertain significance ★★ ⚠ same type
KRT85 p.Gly390Ser Uncertain significance ★★ ⚠ same type
KRT85 p.Gly89Arg Uncertain significance ★★ ⚠ same type
KRT85 c.1078-17G>A Benign/Likely benign ★★ 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/krt85-p-val232met (accessed [today's date]).

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