Is KRT74 p.Val257= (c.771C>T) pathogenic?

KRT74 p.Val257= (c.771C>T) is classified Likely benign in KRT74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). Absent from gnomAD v4.1.

How common is KRT74 p.Val257= (c.771C>T) in the general population?

KRT74 p.Val257= (c.771C>T) is absent from gnomAD v4.1 (gnomAD).

KRT74 p.Val257=

c.771C>T · VCV4917006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.57	phastCons 0.005
Overall
CADD	3.576	PHRED · no single calibrated threshold — expert panels disagree

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: KRT74
Protein: p.Val257=
Coding: c.771C>T
MANE Select: NM_175053
Type: single nucleotide variant
Location: chr12:52571431 (GRCh38)
Gene constraint: LOEUF 1.278 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.11
Residue 257: the if rod domain; the 'coil 1b' region

Full KRT74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT74 p.Val257Asp Benign ★ same residue
KRT74 p.Ala410Thr Uncertain significance ★★ ⚠ same type
KRT74 p.Arg141Gln Uncertain significance ★★ ⚠ same type
KRT74 p.Arg346Gln Uncertain significance ★★ ⚠ same type
KRT74 p.Arg69Trp Uncertain significance ★★ ⚠ same type
KRT74 p.Asp221Val Uncertain significance ★★ ⚠ same type
KRT74 p.Gln426Arg Uncertain significance ★★ ⚠ same type
KRT74 p.Ile7Ser Uncertain significance ★★ ⚠ same type

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/krt74-p-val257 (accessed [today's date]).

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