Is KRT86 p.Ala231Val (c.692C>T) pathogenic?

KRT86 p.Ala231Val (c.692C>T) is classified Uncertain significance in KRT86 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). AlphaMissense: likely benign (0.1475); Very rare (popmax 0.00186%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT86 p.Ala231Val (c.692C>T)?

KRT86 p.Ala231Val (c.692C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT86 p.Ala231Val (c.692C>T) in the general population?

KRT86 p.Ala231Val (c.692C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about KRT86 p.Ala231Val (c.692C>T)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

KRT86 p.Ala231Val

c.692C>T · VCV3289590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.86	GERP 1.9, phastCons 0.001
Regional constraint	o/e 1.06	unconstrained · MANE · 5,286 bp · p 0.28 · regional, not allelic
Overall
CADD	21.4	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 0.00186% European (non-Finnish) · 22/1,180,008 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,614,008 alleles · very rare exomes 18/1,461,852 · genomes 4/152,156 · joint denominator

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: KRT86
Protein: p.Ala231Val
Coding: c.692C>T
MANE Select: NM_001320198
Type: single nucleotide variant
Location: chr12:52304984 (GRCh38)

Full KRT86 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/krt86-p-ala231val (accessed [today's date]).

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