Is KRT9 p.Ile430= (c.1290C>T) pathogenic?

KRT9 p.Ile430= (c.1290C>T) is classified Conflicting classifications of pathogenicity in KRT9 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-07-13). Rare (popmax 0.179%, nfe); Associated with palmoplantar keratoderma, epidermolytic.

What condition is associated with KRT9 p.Ile430= (c.1290C>T)?

KRT9 p.Ile430= (c.1290C>T) is associated with palmoplantar keratoderma, epidermolytic (ClinVar).

How common is KRT9 p.Ile430= (c.1290C>T) in the general population?

KRT9 p.Ile430= (c.1290C>T) is rare (popmax 0.179%, nfe) (gnomAD).

KRT9 p.Ile430=

c.1290C>T · rs145501803 · VCV891512

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.179%, nfe)

Conditions

palmoplantar keratoderma, epidermolytic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.2
Overall
CADD	1.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.179% European (non-Finnish) · 2,112/1,180,036 alleles

Filtering AF 0.173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.142% 2,289/1,613,982 alleles · rare exomes 2,155/1,461,878 · genomes 134/152,104 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.179%	559
Remaining individualsnot grpmax-eligible	0.126%	791
Admixed American	0.0667%	1,500
African / African-American	0.0414%	2,416
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921
Middle Eastern	0.0165%	6,078
South Asian	0.0121%	8,281
Finnishnot grpmax-eligible	0.00937%	10,668
East Asian	0.00891%	11,220

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.Ile430=
Coding: c.1290C>T
MANE Select: NM_000226
dbSNP: rs145501803
Type: single nucleotide variant
Location: chr17:41568266 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 430: the if rod domain; the 'coil 2' region

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

Disease context

palmoplantar keratoderma, epidermolytic — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT9 p.Arg163Gln Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Arg163Trp Pathogenic/Likely pathogenic ★★ same condition
KRT9 p.Asn161Lys Pathogenic/Likely pathogenic ★★ 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

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-ile430 (accessed [today's date]).

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