Is KRT9 p.Ser599= (c.1797C>T) pathogenic?

KRT9 p.Ser599= (c.1797C>T) is classified Uncertain significance in KRT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0267%, eas); Associated with palmoplantar keratoderma, epidermolytic.

What condition is associated with KRT9 p.Ser599= (c.1797C>T)?

KRT9 p.Ser599= (c.1797C>T) is associated with palmoplantar keratoderma, epidermolytic (ClinVar).

How common is KRT9 p.Ser599= (c.1797C>T) in the general population?

KRT9 p.Ser599= (c.1797C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

KRT9 p.Ser599=

c.1797C>T · rs754967566 · VCV889268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Conditions

palmoplantar keratoderma, epidermolytic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.25	GERP -2.2, phastCons 0.002
Overall
CADD	1.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,892 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000806% 13/1,613,518 alleles · ultra-rare exomes 8/1,461,462 · genomes 5/152,056 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Ser599=
Coding: c.1797C>T
MANE Select: NM_000226
dbSNP: rs754967566
Type: single nucleotide variant
Location: chr17:41567348 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 599: the 'disordered' region; the 'tail' 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.Ser599Arg Uncertain significance ★ ⚠ same residue
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

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-ser599 (accessed [today's date]).

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