Is KRT17 p.Arg94Pro (c.281G>C) pathogenic?

KRT17 p.Arg94Pro (c.281G>C) is classified Pathogenic in KRT17 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2001-05-01). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1; Associated with pachyonychia congenita 2.

What condition is associated with KRT17 p.Arg94Pro (c.281G>C)?

KRT17 p.Arg94Pro (c.281G>C) is associated with pachyonychia congenita 2 (ClinVar).

How common is KRT17 p.Arg94Pro (c.281G>C) in the general population?

KRT17 p.Arg94Pro (c.281G>C) is absent from gnomAD v4.1 (gnomAD).

How is Pachyonychia congenita inherited?

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

What do computational predictors say about KRT17 p.Arg94Pro (c.281G>C)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

KRT17 p.Arg94Pro

c.281G>C · rs28928897 · VCV14594

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pachyonychia congenita 2

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic ✓ concordant with ClinVar · top 1% in KRT17
REVEL	0.962	strongly pathogenic-leaning
SaProt	LLR -17.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,912 bp · p 0.082 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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: KRT17
Protein: p.Arg94Pro
Coding: c.281G>C
MANE Select: NM_000422
dbSNP: rs28928897
Type: single nucleotide variant
Location: chr17:41624229 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 94: the if rod domain; a UniProt-annotated variant site (in pc2); a UniProt-annotated variant site (in pc2 and sm); the 'coil 1a' region; a UniProt-annotated variant site (in sm and pc2)

Full KRT17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pachyonychia congenita 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Pachyonychia congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

KRT17 p.Arg94Cys Pathogenic ★★ same residue
KRT17 p.Arg94His Pathogenic/Likely pathogenic ★★ same residue
KRT17 p.Arg94_Tyr98del Pathogenic same residue
KRT17 p.Arg94Leu Likely pathogenic ★★ same residue
KRT17 p.Asn92Asp Pathogenic ★★ same condition
KRT17 p.Asn92Ser Pathogenic ★★ same condition
KRT17 p.Leu99Pro Pathogenic/Likely pathogenic ★★ same condition
KRT17 c.834+5G>A Benign/Likely 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/krt17-p-arg94pro (accessed [today's date]).

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