Is KRT9 p.Ser2Asn (c.5G>A) pathogenic?

KRT9 p.Ser2Asn (c.5G>A) is classified Uncertain significance in KRT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.2771); Very rare (popmax 0.000429%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT9 p.Ser2Asn (c.5G>A)?

KRT9 p.Ser2Asn (c.5G>A) is associated with Inborn genetic diseases (ClinVar).

How common is KRT9 p.Ser2Asn (c.5G>A) in the general population?

KRT9 p.Ser2Asn (c.5G>A) is very rare (popmax 0.000429%, nfe) (gnomAD).

What do computational predictors say about KRT9 p.Ser2Asn (c.5G>A)?

AlphaMissense predicts likely benign (score 0.2771) — an in-silico prediction, not a clinical call.

KRT9 p.Ser2Asn

c.5G>A · VCV4623278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000429%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2771	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP 0.41, phastCons 0.56
Regional constraint	o/e 1.15	unconstrained · MANE · 473 bp · p 0.034 · regional, not allelic
Overall
CADD	18.64	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 0.000429% European (non-Finnish) · 5/1,165,320 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.00035% 5/1,427,570 alleles · very rare

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.Ser2Asn
Coding: c.5G>A
MANE Select: NM_000226
Type: single nucleotide variant
Location: chr17:41571988 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 2: the 'head' region; the 'disordered' 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-ser2asn (accessed [today's date]).

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