Is KRT5 p.Ala525= (c.1575C>T) pathogenic?

KRT5 p.Ala525= (c.1575C>T) is classified Conflicting classifications of pathogenicity in KRT5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-02). Ultra-rare (popmax 0.0268%, amr); Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Ala525= (c.1575C>T)?

KRT5 p.Ala525= (c.1575C>T) is associated with epidermolysis bullosa simplex (ClinVar).

How common is KRT5 p.Ala525= (c.1575C>T) in the general population?

KRT5 p.Ala525= (c.1575C>T) is ultra-rare (popmax 0.0268%, amr) (gnomAD).

KRT5 p.Ala525=

c.1575C>T · rs202104381 · VCV309556

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, amr)

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 -9.7
Overall
CADD	0.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0268% Admixed American · 16/59,608 alleles

Filtering AF 0.0168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00341% 55/1,611,712 alleles · ultra-rare exomes 47/1,459,966 · genomes 8/151,746 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0268%	3,726
African / African-American	0.00535%	18,701
South Asian	0.0044%	22,715
European (non-Finnish)	0.00246%	40,659
East Asian	0.00223%	44,800
Remaining individualsnot grpmax-eligible	0.0016%	62,398

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.Ala525=
Coding: c.1575C>T
MANE Select: NM_000424
dbSNP: rs202104381
Type: single nucleotide variant
Location: chr12:52515140 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 525: a UniProt-annotated variant site (found in a patient with ebs with an unspecified subtype; likely pathogenic); a UniProt-annotated variant site (in ddd1); the 'tail' 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-ala525 (accessed [today's date]).

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