Is KRT17 p.Arg30Pro (c.89G>C) pathogenic?

KRT17 p.Arg30Pro (c.89G>C) is classified Benign/Likely benign in KRT17 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-04). AlphaMissense: likely benign (0.197); Rare (popmax 0.923%, afr).

How common is KRT17 p.Arg30Pro (c.89G>C) in the general population?

KRT17 p.Arg30Pro (c.89G>C) is rare (popmax 0.923%, afr) (gnomAD).

What do computational predictors say about KRT17 p.Arg30Pro (c.89G>C)?

AlphaMissense predicts likely benign (score 0.197) — an in-silico prediction, not a clinical call.

KRT17 p.Arg30Pro

c.89G>C · rs2229512 · VCV2498703

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.197 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.923%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.197	likely benign
REVEL	0.517	indeterminate
SaProt	LLR -10.60	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,912 bp · p 0.082 · regional, not allelic
Overall
CADD	19.92	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

Grpmax group 0.923% African / African-American · 692/74,940 alleles

Filtering AF 0.866% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.844%

Overall 0.07% 1,127/1,610,256 alleles · rare exomes 737/1,457,990 · genomes 390/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.923%	108
Admixed American	0.14%	713
Middle Eastern	0.136%	738
Remaining individualsnot grpmax-eligible	0.0868%	1,152
European (non-Finnish)	0.024%	4,167
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,853
Finnishnot grpmax-eligible	0.00634%	15,767
South Asian	0.0011%	90,938

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.Arg30Pro
Coding: c.89G>C
MANE Select: NM_000422
dbSNP: rs2229512
Type: single nucleotide variant
Location: chr17:41624421 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 30: the 'head' region

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

Similar variants

KRT17 p.Arg30Gln Likely benign ★ same residue
KRT17 p.Arg94Cys Pathogenic ★★ same type
KRT17 p.Arg94His Pathogenic/Likely pathogenic ★★ same type
KRT17 p.Arg94Leu Likely pathogenic ★★ same type
KRT17 p.Asn92Asp Pathogenic ★★ same type
KRT17 p.Asn92Ser Pathogenic ★★ same type
KRT17 p.Leu99Pro Pathogenic/Likely pathogenic ★★ same type
KRT17 p.Arg406Cys Uncertain significance ★★ ⚠ same type

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-arg30pro (accessed [today's date]).

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