Is KRT9 p.Arg34His (c.101G>A) pathogenic?

KRT9 p.Arg34His (c.101G>A) is classified Uncertain significance in KRT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1766); Ultra-rare (popmax 0.0353%, mid); Associated with Inborn genetic diseases.

What condition is associated with KRT9 p.Arg34His (c.101G>A)?

KRT9 p.Arg34His (c.101G>A) is associated with Inborn genetic diseases (ClinVar).

How common is KRT9 p.Arg34His (c.101G>A) in the general population?

KRT9 p.Arg34His (c.101G>A) is ultra-rare (popmax 0.0353%, mid) (gnomAD).

What do computational predictors say about KRT9 p.Arg34His (c.101G>A)?

AlphaMissense predicts likely benign (score 0.1766) — an in-silico prediction, not a clinical call.

KRT9 p.Arg34His

c.101G>A · rs146238717 · VCV2593785

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0353%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1766	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -9.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.006	GERP 0.79
Regional constraint	o/e 1.15	unconstrained · MANE · 473 bp · p 0.034 · regional, not allelic
Overall
CADD	18.12	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 0.0353% Middle Eastern · 2/5,658 alleles

Filtering AF 0.0236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0227%

Overall 0.0213% 342/1,609,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0353%	2,829
European (non-Finnish)	0.0261%	3,838
South Asian	0.0199%	5,019
Remaining individualsnot grpmax-eligible	0.0129%	7,779
Admixed American	0.00503%	19,873
African / African-American	0.00268%	37,343
East Asian	0.00224%	44,710
Finnishnot grpmax-eligible	0.00158%	63,432

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.Arg34His
Coding: c.101G>A
MANE Select: NM_000226
dbSNP: rs146238717
Type: single nucleotide variant
Location: chr17:41571892 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 34: the 'head' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT9 p.Arg13His Uncertain significance ★★ ⚠ 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
KRT9 p.Ser357Pro Uncertain significance ★★ ⚠ same condition
KRT9 p.Ser8Leu 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-arg34his (accessed [today's date]).

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