Is KRT5 p.Ala357= (c.1071C>T) pathogenic?

KRT5 p.Ala357= (c.1071C>T) is classified Benign/Likely benign in KRT5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-01). Rare (popmax 0.626%, nfe); Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Ala357= (c.1071C>T)?

KRT5 p.Ala357= (c.1071C>T) is associated with epidermolysis bullosa simplex (ClinVar).

How common is KRT5 p.Ala357= (c.1071C>T) in the general population?

KRT5 p.Ala357= (c.1071C>T) is rare (popmax 0.626%, nfe) (gnomAD).

KRT5 p.Ala357=

c.1071C>T · rs149467228 · VCV309563

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.626%, nfe)

Conditions

epidermolysis bullosa simplex

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 -5.3
Overall
CADD	4.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.626% European (non-Finnish) · 7,390/1,180,016 alleles

Filtering AF 0.614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.609%

Overall 0.556% 8,972/1,614,124 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.19%	84
European (non-Finnish)grpmax	0.626%	160
Remaining individualsnot grpmax-eligible	0.453%	221
Ashkenazi Jewishnot grpmax-eligible	0.453%	221
Middle Eastern	0.281%	356
Admixed American	0.273%	366
South Asian	0.18%	555
African / African-American	0.08%	1,251

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KRT5
Protein: p.Ala357=
Coding: c.1071C>T
MANE Select: NM_000424
dbSNP: rs149467228
Type: single nucleotide variant
Location: chr12:52517611 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 357: the if rod domain; a UniProt-annotated variant site (in ddd1); the 'coil 2' region

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 condition
KRT5 p.Ala428Val Pathogenic/Likely pathogenic ★★ same condition
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

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-ala357 (accessed [today's date]).

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