Is KRT5 p.Ala428Val (c.1283C>T) pathogenic?

KRT5 p.Ala428Val (c.1283C>T) is classified Pathogenic/Likely pathogenic in KRT5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-13). AlphaMissense: likely pathogenic (0.9729); Absent from gnomAD v4.1; Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Ala428Val (c.1283C>T)?

KRT5 p.Ala428Val (c.1283C>T) is associated with epidermolysis bullosa simplex (ClinVar).

How common is KRT5 p.Ala428Val (c.1283C>T) in the general population?

KRT5 p.Ala428Val (c.1283C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT5 p.Ala428Val (c.1283C>T)?

AlphaMissense predicts likely pathogenic (score 0.9729) — an in-silico prediction, not a clinical call.

KRT5 p.Ala428Val

c.1283C>T · rs59243757 · VCV66203

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epidermolysis bullosa simplex

Computational evidence

Protein change
AlphaMissense	0.9729	likely pathogenic ✓ concordant with ClinVar
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -13.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,753 bp · p 0.69 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KRT5
Protein: p.Ala428Val
Coding: c.1283C>T
MANE Select: NM_000424
dbSNP: rs59243757
Type: single nucleotide variant
Location: chr12:52516793 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 428: the if rod domain; an α-helix; a UniProt-annotated variant site (in ddd1); the 'coil 2' region; a UniProt-annotated variant site (in ebs2c)

Full KRT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa simplex — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT5 p.Ala428Thr Pathogenic/Likely pathogenic ★★ same residue
KRT5 p.Glu170Lys Pathogenic ★★ same condition
KRT5 p.Glu466Gln Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Glu477Lys Pathogenic ★★ same condition
KRT5 p.Leu196Pro Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Leu463Pro Pathogenic ★★ same condition
KRT5 p.Pro25Leu Pathogenic ★★ same condition
KRT5 p.Val186Met Pathogenic ★★ 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/krt5-p-ala428val (accessed [today's date]).

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