Is KRT9 p.Arg327Cys (c.979C>T) pathogenic?

KRT9 p.Arg327Cys (c.979C>T) is classified Uncertain significance in KRT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely pathogenic (0.8781); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with KRT9 p.Arg327Cys (c.979C>T)?

KRT9 p.Arg327Cys (c.979C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT9 p.Arg327Cys (c.979C>T) in the general population?

KRT9 p.Arg327Cys (c.979C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about KRT9 p.Arg327Cys (c.979C>T)?

AlphaMissense predicts likely pathogenic (score 0.8781) — an in-silico prediction, not a clinical call.

KRT9 p.Arg327Cys

c.979C>T · rs767325538 · VCV2344587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8781 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8781	likely pathogenic · top 8% in KRT9
REVEL	0.714	pathogenic-leaning
SaProt	LLR -10.52	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 1.7	GERP 2.1, phastCons 0.97
Regional constraint	o/e 0.90	unconstrained · MANE · 4,200 bp · p 0.017 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00124% 20/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
African / African-American	0.00667%	14,983
East Asian	0.00223%	44,900
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,080
European (non-Finnish)	0.000763%	131,109

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.Arg327Cys
Coding: c.979C>T
MANE Select: NM_000226
dbSNP: rs767325538
Type: single nucleotide variant
Location: chr17:41569491 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 327: the if rod domain; the 'coil 2' 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.Arg327His Uncertain significance ★★ ⚠ same residue
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

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-arg327cys (accessed [today's date]).

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