Is KRT5 p.Cys135Phe (c.404G>T) pathogenic?

KRT5 p.Cys135Phe (c.404G>T) is classified Uncertain significance in KRT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: ambiguous (0.3612); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KRT5 p.Cys135Phe (c.404G>T)?

KRT5 p.Cys135Phe (c.404G>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT5 p.Cys135Phe (c.404G>T) in the general population?

KRT5 p.Cys135Phe (c.404G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT5 p.Cys135Phe (c.404G>T)?

AlphaMissense predicts ambiguous (score 0.3612) — an in-silico prediction, not a clinical call.

KRT5 p.Cys135Phe

c.404G>T · VCV3865573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3612 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3612	ambiguous
REVEL	0.548	indeterminate
SaProt	LLR -10.10	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,321 bp · p 0.7 · regional, not allelic
Overall
CADD	25.6	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.Cys135Phe
Coding: c.404G>T
MANE Select: NM_000424
Type: single nucleotide variant
Location: chr12:52519893 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 135: the 'head' region; a UniProt-annotated variant site (in ddd1)

Full KRT5 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

KRT5 p.Cys135Ter Likely pathogenic ★ same residue
KRT5 p.Pro25Leu Pathogenic ★★ same condition
KRT5 p.Ala101Thr Uncertain significance ★★ ⚠ same condition
KRT5 p.Ala20Thr Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg169His Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg239Cys Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg354Trp Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg559Gln 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/krt5-p-cys135phe (accessed [today's date]).

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