Is KRT4 p.Leu55= (c.165C>T) pathogenic?

KRT4 p.Leu55= (c.165C>T) is classified Likely benign in KRT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Very rare (popmax 0.00129%, nfe).

How common is KRT4 p.Leu55= (c.165C>T) in the general population?

KRT4 p.Leu55= (c.165C>T) is very rare (popmax 0.00129%, nfe) (gnomAD).

KRT4 p.Leu55=

c.165C>T · VCV4917053

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00129%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.2	GERP -3.8
Overall
CADD	0.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00129% European (non-Finnish) · 12/928,806 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000544%

Overall 0.00105% 12/1,147,270 alleles · very rare exomes 11/1,119,364 · genomes 1/27,906 · joint denominator

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: KRT4
Protein: p.Leu55=
Coding: c.165C>T
MANE Select: NM_002272
Type: single nucleotide variant
Location: chr12:52813894 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 55: the 'head' region

Full KRT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT4 p.Leu55Pro Uncertain significance ★ ⚠ same residue
KRT4 p.Ala106Gly Uncertain significance ★★ ⚠ same type
KRT4 p.Asp153Asn Uncertain significance ★★ ⚠ same type
KRT4 p.Asp247Glu Uncertain significance ★★ same type
KRT4 c.1126-32G>A Benign ★★ same type
KRT4 c.1346+15A>G Benign ★★ same type
KRT4 c.1346+15A>T Likely benign ★★ same type
KRT4 c.1381+15C>T Benign ★★ 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/krt4-p-leu55 (accessed [today's date]).

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