Is KRT86 p.Val286Phe (c.856G>T) pathogenic?

KRT86 p.Val286Phe (c.856G>T) is classified Uncertain significance in KRT86 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: ambiguous (0.42); Ultra-rare (popmax 0.0657%, mid); Associated with Inborn genetic diseases.

What condition is associated with KRT86 p.Val286Phe (c.856G>T)?

KRT86 p.Val286Phe (c.856G>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT86 p.Val286Phe (c.856G>T) in the general population?

KRT86 p.Val286Phe (c.856G>T) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about KRT86 p.Val286Phe (c.856G>T)?

AlphaMissense predicts ambiguous (score 0.42) — an in-silico prediction, not a clinical call.

KRT86 p.Val286Phe

c.856G>T · rs780785303 · VCV2350058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.42 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.42	ambiguous
REVEL	0.614	indeterminate
SaProt	LLR -9.78	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 5,286 bp · p 0.28 · regional, not allelic
Overall
CADD	23.2	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00173% 28/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
African / African-American	0.0107%	9,368
Remaining individualsnot grpmax-eligible	0.0032%	31,245
South Asian	0.0022%	45,546
European (non-Finnish)	0.00102%	98,337

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.Val286Phe
Coding: c.856G>T
MANE Select: NM_001320198
dbSNP: rs780785303
Type: single nucleotide variant
Location: chr12:52305360 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50
Residue 286: the if rod domain; the 'coil 2' region

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

Similar variants

KRT86 p.Val286Ile Uncertain significance ★ ⚠ same residue
KRT86 p.Ala293Asp Uncertain significance ★★ ⚠ same condition
KRT86 p.Ala218Thr Uncertain significance ★ ⚠ same condition
KRT86 p.Ala360Ser Uncertain significance ★ ⚠ same condition
KRT86 p.Ala383Asp Uncertain significance ★ ⚠ same condition
KRT86 p.Ala404Thr Uncertain significance ★ ⚠ same condition
KRT86 p.Ala446Asp Uncertain significance ★ ⚠ same condition
KRT86 p.Arg21Pro 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/krt86-p-val286phe (accessed [today's date]).

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