Is KRT9 p.Leu285= (c.855G>T) pathogenic?

KRT9 p.Leu285= (c.855G>T) is classified Benign/Likely benign in KRT9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.49%, afr); Associated with palmoplantar keratoderma, epidermolytic.

What condition is associated with KRT9 p.Leu285= (c.855G>T)?

KRT9 p.Leu285= (c.855G>T) is associated with palmoplantar keratoderma, epidermolytic (ClinVar).

How common is KRT9 p.Leu285= (c.855G>T) in the general population?

KRT9 p.Leu285= (c.855G>T) is low-frequency (popmax 1.49%, afr) (gnomAD).

KRT9 p.Leu285=

c.855G>T · rs115349045 · VCV889334

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, afr)

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 1.3	GERP 1.1, phastCons 0.018
Overall
CADD	4.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.49% African / African-American · 1,116/75,046 alleles

Filtering AF 1.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.105% 1,690/1,614,202 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.49%	67
Middle Eastern	0.429%	233
Admixed American	0.172%	583
Remaining individualsnot grpmax-eligible	0.17%	590
European (non-Finnish)	0.0271%	3,688
South Asian	0.0198%	5,060
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Leu285=
Coding: c.855G>T
MANE Select: NM_000226
dbSNP: rs115349045
Type: single nucleotide variant
Location: chr17:41569886 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 285: the if rod domain; the 'coil 1b' 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-leu285 (accessed [today's date]).

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