Is KRT9 p.Ser14= (c.42C>T) pathogenic?

KRT9 p.Ser14= (c.42C>T) is classified Benign in KRT9 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 6.58%, amr) — too common for a highly-penetrant pathogenic allele; Associated with palmoplantar keratoderma, epidermolytic.

What condition is associated with KRT9 p.Ser14= (c.42C>T)?

KRT9 p.Ser14= (c.42C>T) is associated with palmoplantar keratoderma, epidermolytic (ClinVar).

KRT9 p.Ser14=

Q: How common is KRT9 p.Ser14= (c.42C>T) in the general population?

KRT9 p.Ser14= (c.42C>T) is common (popmax 6.58%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.42C>T · rs116077803 · VCV323143

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.58%, amr) — too common for a highly-penetrant pathogenic allele

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 -0.54	GERP -0.49
Overall
CADD	3.851	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.58% Admixed American · 3,693/56,158 alleles

Filtering AF 6.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.33%

Overall 1.19% 18,868/1,584,034 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	6.58%	15
Amishnot grpmax-eligible	2.3%	43
Ashkenazi Jewishnot grpmax-eligible	1.72%	58
Remaining individualsnot grpmax-eligible	1.36%	73
European (non-Finnish)	1.12%	89
Middle Eastern	0.652%	153
Finnishnot grpmax-eligible	0.42%	238
South Asian	0.303%	330
African / African-American	0.283%	353
East Asian	0.00228%	43,858

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.Ser14=
Coding: c.42C>T
MANE Select: NM_000226
dbSNP: rs116077803
Type: single nucleotide variant
Location: chr17:41571951 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 14: a modified residue (phosphoserine); 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-ser14 (accessed [today's date]).

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