Is KRT9 p.Ser24= (c.72C>T) pathogenic?

KRT9 p.Ser24= (c.72C>T) is classified Benign/Likely benign in KRT9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-30). Rare (popmax 0.889%, sas); Associated with palmoplantar keratoderma, epidermolytic.

What condition is associated with KRT9 p.Ser24= (c.72C>T)?

KRT9 p.Ser24= (c.72C>T) is associated with palmoplantar keratoderma, epidermolytic (ClinVar).

How common is KRT9 p.Ser24= (c.72C>T) in the general population?

KRT9 p.Ser24= (c.72C>T) is rare (popmax 0.889%, sas) (gnomAD).

KRT9 p.Ser24=

c.72C>T · rs369925340 · VCV323142

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.889%, sas)

Conditions

palmoplantar keratoderma, epidermolytic

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 -3.2	GERP -1.8
Overall
CADD	0.323	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.889% South Asian · 784/88,140 alleles

Filtering AF 0.838% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.817%

Overall 0.0538% 855/1,588,704 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.889%	112
Remaining individualsnot grpmax-eligible	0.0685%	1,461
East Asian	0.0228%	4,380
Middle Eastern	0.0213%	4,690
African / African-American	0.00808%	12,379
Admixed American	0.0035%	28,575
European (non-Finnish)	0.000856%	116,832

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: KRT9
Protein: p.Ser24=
Coding: c.72C>T
MANE Select: NM_000226
dbSNP: rs369925340
Type: single nucleotide variant
Location: chr17:41571921 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 24: the 'head' region; the 'disordered' region

Full KRT9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

KRT9 p.Arg163Gln Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Arg163Trp Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Asn161Lys Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Gly116Asp Uncertain significance ★★ ⚠ same condition
KRT9 p.Gly193Glu Uncertain significance ★★ ⚠ same condition
KRT9 p.Gly507Arg Uncertain significance ★★ same condition
KRT9 p.Gly507Val Uncertain significance ★★ ⚠ same condition
KRT9 p.Ile341Val Uncertain significance ★★ ⚠ 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/krt9-p-ser24 (accessed [today's date]).

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