Is KRT5 p.Arg48= (c.142A>C) pathogenic?

KRT5 p.Arg48= (c.142A>C) is classified Benign in KRT5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Common (popmax 6.97%, afr) — too common for a highly-penetrant pathogenic allele; Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Arg48= (c.142A>C)?

KRT5 p.Arg48= (c.142A>C) is associated with epidermolysis bullosa simplex (ClinVar).

KRT5 p.Arg48=

Q: How common is KRT5 p.Arg48= (c.142A>C) in the general population?

KRT5 p.Arg48= (c.142A>C) is common (popmax 6.97%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.142A>C · rs61747180 · VCV309572

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.97%, afr) — 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 1.5	phastCons 1
Overall
CADD	8.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.97% African / African-American · 5,225/74,986 alleles

Filtering AF 6.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.75%

Overall 0.431% 6,949/1,613,776 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.97%	14
Middle Eastern	1.37%	73
Ashkenazi Jewishnot grpmax-eligible	0.804%	124
Admixed American	0.691%	145
Remaining individualsnot grpmax-eligible	0.682%	147
European (non-Finnish)	0.0451%	2,218
South Asian	0.0318%	3,140
Finnishnot grpmax-eligible	0.00156%	63,966

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.Arg48=
Coding: c.142A>C
MANE Select: NM_000424
dbSNP: rs61747180
Type: single nucleotide variant
Location: chr12:52520155 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 48: 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-arg48 (accessed [today's date]).

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