Is KRT9 p.Phe97= (c.291T>C) pathogenic?

KRT9 p.Phe97= (c.291T>C) is classified Uncertain significance in KRT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00539%, afr); Associated with palmoplantar keratoderma, epidermolytic.

What condition is associated with KRT9 p.Phe97= (c.291T>C)?

KRT9 p.Phe97= (c.291T>C) is associated with palmoplantar keratoderma, epidermolytic (ClinVar).

How common is KRT9 p.Phe97= (c.291T>C) in the general population?

KRT9 p.Phe97= (c.291T>C) is very rare (popmax 0.00539%, afr) (gnomAD).

KRT9 p.Phe97=

c.291T>C · rs376830738 · VCV891573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00539%, afr)

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 -1.1	GERP -3.2
Overall
CADD	0.641	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00539% African / African-American · 4/74,232 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00131% 21/1,608,616 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00539%	18,558
European (non-Finnish)	0.00144%	69,273

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.Phe97=
Coding: c.291T>C
MANE Select: NM_000226
dbSNP: rs376830738
Type: single nucleotide variant
Location: chr17:41571702 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 97: the 'head' 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-phe97 (accessed [today's date]).

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