Is KRT5 p.Thr19= (c.57C>T) pathogenic?

KRT5 p.Thr19= (c.57C>T) is classified Benign in KRT5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Rare (popmax 0.242%, sas); Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Thr19= (c.57C>T)?

KRT5 p.Thr19= (c.57C>T) is associated with epidermolysis bullosa simplex (ClinVar).

How common is KRT5 p.Thr19= (c.57C>T) in the general population?

KRT5 p.Thr19= (c.57C>T) is rare (popmax 0.242%, sas) (gnomAD).

KRT5 p.Thr19=

c.57C>T · rs529397720 · VCV790862

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.242%, sas)

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 -6.7
Overall
CADD	1.844	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.242% South Asian · 220/91,068 alleles

Filtering AF 0.215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0159% 256/1,613,988 alleles · rare exomes 238/1,461,692 · genomes 18/152,296 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.242%	414
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0144%	6,945
African / African-American	0.00533%	18,765
East Asian	0.00446%	22,434
Admixed American	0.00333%	30,014
European (non-Finnish)	0.00153%	65,557

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.Thr19=
Coding: c.57C>T
MANE Select: NM_000424
dbSNP: rs529397720
Type: single nucleotide variant
Location: chr12:52520240 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 19: the 'head' region; a UniProt-annotated variant site (in ddd1); the 'disordered' 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.Thr19Ile 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
KRT5 p.Leu463Pro 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-thr19 (accessed [today's date]).

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