Is KRT5 p.Phe87Val (c.259T>G) pathogenic?

KRT5 p.Phe87Val (c.259T>G) is classified Benign in KRT5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1651); Common (popmax 5.76%, afr) — too common for a highly-penetrant pathogenic allele; Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Phe87Val (c.259T>G)?

KRT5 p.Phe87Val (c.259T>G) is associated with epidermolysis bullosa simplex (ClinVar).

What do computational predictors say about KRT5 p.Phe87Val (c.259T>G)?

AlphaMissense predicts likely benign (score 0.1651) — an in-silico prediction, not a clinical call.

KRT5 p.Phe87Val

Q: How common is KRT5 p.Phe87Val (c.259T>G) in the general population?

KRT5 p.Phe87Val (c.259T>G) is common (popmax 5.76%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.259T>G · rs61747188 · VCV309571

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1651 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.76%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epidermolysis bullosa simplex

Computational evidence

Protein change
AlphaMissense	0.1651	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	phastCons 0.029
Regional constraint	o/e 0.98	unconstrained · MANE · 1,321 bp · p 0.7 · regional, not allelic
Overall
CADD	15.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.76% African / African-American · 4,309/74,768 alleles

Filtering AF 5.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.56%

Overall 0.295% 4,755/1,613,422 alleles · common exomes 2,295/1,461,868 · genomes 2,460/151,554 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.76%	17
Remaining individualsnot grpmax-eligible	0.365%	274
Admixed American	0.285%	351
Middle Eastern	0.0825%	1,212
South Asian	0.0176%	5,688
European (non-Finnish)	0.0022%	45,379

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.Phe87Val
Coding: c.259T>G
MANE Select: NM_000424
dbSNP: rs61747188
Type: single nucleotide variant
Location: chr12:52520038 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 87: 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.Phe87Cys Uncertain significance ★ ⚠ same residue
KRT5 p.Phe87Leu Uncertain significance ★ ⚠ same residue
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

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-phe87val (accessed [today's date]).

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