Is KRT1 p.Val155Asp (c.464T>A) pathogenic?

KRT1 p.Val155Asp (c.464T>A) is classified Pathogenic in KRT1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2001-08-01). AlphaMissense: likely pathogenic (0.9912); Absent from gnomAD v4.1; Associated with epidermolytic ichthyosis.

What condition is associated with KRT1 p.Val155Asp (c.464T>A)?

KRT1 p.Val155Asp (c.464T>A) is associated with epidermolytic ichthyosis (ClinVar).

How common is KRT1 p.Val155Asp (c.464T>A) in the general population?

KRT1 p.Val155Asp (c.464T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT1 p.Val155Asp (c.464T>A)?

AlphaMissense predicts likely pathogenic (score 0.9912) — an in-silico prediction, not a clinical call.

KRT1 p.Val155Asp

c.464T>A · rs57959072 · VCV15913

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9912 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epidermolytic ichthyosis

Computational evidence

Protein change
AlphaMissense	0.9912	likely pathogenic ✓ concordant with ClinVar · top 4% in KRT1
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -16.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,152 bp · p 0.25 · regional, not allelic
Overall
CADD	28.8	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

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: KRT1
Protein: p.Val155Asp
Coding: c.464T>A
MANE Select: NM_006121
dbSNP: rs57959072
Type: single nucleotide variant
Location: chr12:52679885 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.62 · 3 PDB
Residue 155: the 'head' region; a UniProt-annotated variant site (in ehk1)

Full KRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolytic ichthyosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT1 p.Asn188Lys Pathogenic ★★ same condition
KRT1 p.Leu485Phe Pathogenic/Likely pathogenic ★★ same condition
KRT1 p.Arg86His Uncertain significance ★★ ⚠ same condition
KRT1 p.Gly556Ser Uncertain significance ★★ ⚠ same condition
KRT1 c.1511-11T>C Benign/Likely benign ★★ same condition
KRT1 c.592-8G>A Benign/Likely benign ★★ same condition
KRT1 c.*344C>T Benign ★★ same condition
KRT1 p.Ala369= Benign/Likely benign ★★ 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/krt1-p-val155asp (accessed [today's date]).

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