Is KRT6B p.Val282Phe (c.844G>T) pathogenic?

KRT6B p.Val282Phe (c.844G>T) is classified Uncertain significance in KRT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: ambiguous (0.4783); Ultra-rare (popmax 0.0115%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT6B p.Val282Phe (c.844G>T)?

KRT6B p.Val282Phe (c.844G>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT6B p.Val282Phe (c.844G>T) in the general population?

KRT6B p.Val282Phe (c.844G>T) is ultra-rare (popmax 0.0115%, nfe) (gnomAD).

What do computational predictors say about KRT6B p.Val282Phe (c.844G>T)?

AlphaMissense predicts ambiguous (score 0.4783) — an in-silico prediction, not a clinical call.

KRT6B p.Val282Phe

c.844G>T · VCV4045062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0115%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4783	ambiguous
REVEL	0.618	indeterminate
SaProt	LLR -14.99	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.015	GERP -0.081
Regional constraint	o/e 1.05	unconstrained · MANE · 3,349 bp · p 0.25 · regional, not allelic
Overall
CADD	22.1	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 0.0115% European (non-Finnish) · 136/1,179,894 alleles

Filtering AF 0.00994% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00931%

Overall 0.00911% 147/1,613,974 alleles · ultra-rare exomes 137/1,461,706 · genomes 10/152,268 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,812
European (non-Finnish)grpmax	0.0115%	8,676
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
African / African-American	0.00267%	37,517

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KRT6B
Protein: p.Val282Phe
Coding: c.844G>T
MANE Select: NM_005555
Type: single nucleotide variant
Location: chr12:52449826 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.76
Residue 282: the if rod domain; the 'coil 1b' region

Full KRT6B 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

KRT6B p.Ala403Val Uncertain significance ★★ ⚠ same condition
KRT6B p.Arg260His Uncertain significance ★★ same condition
KRT6B p.Arg375His Uncertain significance ★★ ⚠ same condition
KRT6B p.Arg386His Uncertain significance ★★ same condition
KRT6B p.Gln208His Uncertain significance ★★ ⚠ same condition
KRT6B p.Gln379Arg Uncertain significance ★★ ⚠ same condition
KRT6B p.Gly103Ser Uncertain significance ★★ ⚠ same condition
KRT6B p.Lys281Gln 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/krt6b-p-val282phe (accessed [today's date]).

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