Is KRT5 p.Ala52= (c.156G>A) pathogenic?

KRT5 p.Ala52= (c.156G>A) is classified Benign in KRT5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 5.65%, amr) — too common for a highly-penetrant pathogenic allele; Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Ala52= (c.156G>A)?

KRT5 p.Ala52= (c.156G>A) is associated with epidermolysis bullosa simplex (ClinVar).

KRT5 p.Ala52=

Q: How common is KRT5 p.Ala52= (c.156G>A) in the general population?

KRT5 p.Ala52= (c.156G>A) is common (popmax 5.65%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.156G>A · rs74093478 · VCV256041

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 5.65%, amr) — too common for a highly-penetrant pathogenic allele

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 -0.02	phastCons 0.093
Overall
CADD	9.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.65% Admixed American · 3,391/60,016 alleles

Filtering AF 5.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.43%

Overall 0.728% 11,743/1,613,934 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	5.65%	18
African / African-American	4.6%	22
Middle Eastern	1.17%	85
South Asian	1.13%	88
East Asian	0.889%	112
Remaining individualsnot grpmax-eligible	0.851%	117
European (non-Finnish)	0.242%	412
Finnishnot grpmax-eligible	0.00938%	10,661
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800

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.Ala52=
Coding: c.156G>A
MANE Select: NM_000424
dbSNP: rs74093478
Type: single nucleotide variant
Location: chr12:52520141 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 52: 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

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-ala52 (accessed [today's date]).

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