Is KRT1 p.Ser247= (c.741T>C) pathogenic?

KRT1 p.Ser247= (c.741T>C) is classified Benign in KRT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-30). Low-frequency (popmax 3.46%, afr); Associated with diffuse nonepidermolytic palmoplantar keratoderma.

How common is KRT1 p.Ser247= (c.741T>C) in the general population?

KRT1 p.Ser247= (c.741T>C) is low-frequency (popmax 3.46%, afr) (gnomAD).

KRT1 p.Ser247=

Q: What condition is associated with KRT1 p.Ser247= (c.741T>C)?

KRT1 p.Ser247= (c.741T>C) is associated with diffuse nonepidermolytic palmoplantar keratoderma, epidermolytic ichthyosis (ClinVar).

Q: How is KRT1-related diffuse nonepidermolytic keratoderma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.741T>C · rs56895471 · VCV309650

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.46%, afr)

Conditions

diffuse nonepidermolytic palmoplantar keratoderma

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 -7.3	GERP -3.7
Overall
CADD	0.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.46% African / African-American · 2,593/75,022 alleles

Filtering AF 3.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.3%

Overall 0.179% 2,897/1,614,128 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.46%	29
Admixed American	0.21%	476
Remaining individualsnot grpmax-eligible	0.21%	477
Middle Eastern	0.0165%	6,062
South Asian	0.00659%	15,179
European (non-Finnish)	0.00339%	29,501

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: KRT1
Protein: p.Ser247=
Coding: c.741T>C
MANE Select: NM_006121
dbSNP: rs56895471
Type: single nucleotide variant
Location: chr12:52678607 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.62 · 3 PDB
Residue 247: the if rod domain; the 'coil 1b' region; an α-helix

Full KRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

diffuse nonepidermolytic palmoplantar keratoderma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolytic ichthyosis

For KRT1-related diffuse nonepidermolytic keratoderma (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

Similar variants

KRT1 c.1255-1G>T Pathogenic ★★ same condition
KRT1 p.Asn188Lys Pathogenic ★★ same condition
KRT1 p.Leu485Phe Pathogenic/Likely pathogenic ★★ same condition
KRT1 p.Arg86His Uncertain significance ★★ ⚠ same condition
KRT1 p.Gly556Ser Uncertain significance ★★ ⚠ same condition
KRT1 c.1511-11T>C Benign/Likely benign ★★ same condition
KRT1 c.592-8G>A Benign/Likely benign ★★ same condition
KRT1 c.*344C>T Benign ★★ 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/krt1-p-ser247 (accessed [today's date]).

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