Is KRT17 p.Arg26Pro (c.77G>C) pathogenic?

KRT17 p.Arg26Pro (c.77G>C) is classified Uncertain significance in KRT17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.2511); Very rare (popmax 0.0011%, sas); Associated with sebocystomatosis.

What condition is associated with KRT17 p.Arg26Pro (c.77G>C)?

KRT17 p.Arg26Pro (c.77G>C) is associated with sebocystomatosis (ClinVar).

How common is KRT17 p.Arg26Pro (c.77G>C) in the general population?

KRT17 p.Arg26Pro (c.77G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Sebocystomatosis inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KRT17 p.Arg26Pro (c.77G>C)?

AlphaMissense predicts likely benign (score 0.2511) — an in-silico prediction, not a clinical call.

KRT17 p.Arg26Pro

c.77G>C · VCV4278037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2511 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

sebocystomatosis

Computational evidence

Protein change
AlphaMissense	0.2511	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.47, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 4,912 bp · p 0.082 · regional, not allelic
Overall
CADD	19.99	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0011% South Asian · 1/90,894 alleles

Overall 6.21e-05% 1/1,609,974 alleles · very rare exomes 1/1,457,674 · genomes 0/152,300 · joint denominator

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: KRT17
Protein: p.Arg26Pro
Coding: c.77G>C
MANE Select: NM_000422
Type: single nucleotide variant
Location: chr17:41624433 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 26: the 'head' region

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

Disease context

sebocystomatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sebocystomatosis (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood

Similar variants

KRT17 p.Arg94Cys Pathogenic ★★ same condition
KRT17 p.Arg94His Pathogenic/Likely pathogenic ★★ same condition
KRT17 p.Asn92Ser Pathogenic ★★ same condition
KRT17 c.834+5G>A Benign/Likely benign ★★ same condition
KRT17 p.Arg180Ser Uncertain significance ★ ⚠ same condition
KRT17 p.Arg385Cys Uncertain significance ★ ⚠ same condition
KRT17 p.Lys262Ter Conflicting classifications of pathogenicity ★ same condition
KRT17 p.Ser301Leu 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/krt17-p-arg26pro (accessed [today's date]).

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