Is KRT5 p.Val234= (c.702G>T) pathogenic?

KRT5 p.Val234= (c.702G>T) is classified Uncertain significance in KRT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00667%, afr); Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Val234= (c.702G>T)?

KRT5 p.Val234= (c.702G>T) is associated with epidermolysis bullosa simplex (ClinVar).

How common is KRT5 p.Val234= (c.702G>T) in the general population?

KRT5 p.Val234= (c.702G>T) is very rare (popmax 0.00667%, afr) (gnomAD).

KRT5 p.Val234=

c.702G>T · rs149863112 · VCV309566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Conditions

epidermolysis bullosa simplex

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.055	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11
Overall
CADD	0.089	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,936 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000929% 15/1,614,090 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,987
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000678%	147,507

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.Val234=
Coding: c.702G>T
MANE Select: NM_000424
dbSNP: rs149863112
Type: single nucleotide variant
Location: chr12:52519014 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 234: the if rod domain; a UniProt-annotated variant site (in ddd1); the 'coil 1b' 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-val234 (accessed [today's date]).

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