Is KRT9 p.Ser162Pro (c.484T>C) pathogenic?

KRT9 p.Ser162Pro (c.484T>C) is classified Uncertain significance in KRT9 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-23). AlphaMissense: likely pathogenic (0.9502); Absent from gnomAD v4.1; Associated with epidermolytic palmoplantar keratoderma, 1.

What condition is associated with KRT9 p.Ser162Pro (c.484T>C)?

KRT9 p.Ser162Pro (c.484T>C) is associated with epidermolytic palmoplantar keratoderma, 1 (ClinVar).

How common is KRT9 p.Ser162Pro (c.484T>C) in the general population?

KRT9 p.Ser162Pro (c.484T>C) is absent from gnomAD v4.1 (gnomAD).

How is Epidermolytic palmoplantar keratoderma inherited?

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

What do computational predictors say about KRT9 p.Ser162Pro (c.484T>C)?

AlphaMissense predicts likely pathogenic (score 0.9502) — an in-silico prediction, not a clinical call.

KRT9 p.Ser162Pro

c.484T>C · rs267607419 · VCV66155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9502 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

epidermolytic palmoplantar keratoderma, 1

Computational evidence

Protein change
AlphaMissense	0.9502	likely pathogenic · top 4% in KRT9
REVEL	0.488	indeterminate
SaProt	LLR -10.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.2
Regional constraint	o/e 0.31	constrained · MANE · 41 bp · p 0.0051 · regional, not allelic
Overall
CADD	13.18	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KRT9
Protein: p.Ser162Pro
Coding: c.484T>C
MANE Select: NM_000226
dbSNP: rs267607419
Type: single nucleotide variant
Location: chr17:41571509 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 162: the if rod domain; the 'coil 1a' region

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

Disease context

epidermolytic palmoplantar keratoderma, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Epidermolytic palmoplantar keratoderma (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Ireland)

Similar variants

KRT9 p.Arg163Gln Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Arg163Leu Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Arg163Trp Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Asn161Lys Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Asn161Ser Pathogenic ★★ same condition
KRT9 p.Met157Val Pathogenic ★★ same condition
KRT9 p.Arg327His Uncertain significance ★★ ⚠ same condition
KRT9 p.Leu160Val Likely 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/krt9-p-ser162pro (accessed [today's date]).

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