Is KRT9 p.Ser623= (c.1869C>T) pathogenic?

KRT9 p.Ser623= (c.1869C>T) is classified Conflicting classifications of pathogenicity in KRT9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-23). Ultra-rare (popmax 0.0329%, mid); Associated with palmoplantar keratoderma, epidermolytic.

What condition is associated with KRT9 p.Ser623= (c.1869C>T)?

KRT9 p.Ser623= (c.1869C>T) is associated with palmoplantar keratoderma, epidermolytic (ClinVar).

How common is KRT9 p.Ser623= (c.1869C>T) in the general population?

KRT9 p.Ser623= (c.1869C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

KRT9 p.Ser623=

c.1869C>T · rs749243428 · VCV889267

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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 0.8	GERP 0.23, phastCons 1
Overall
CADD	4.757	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00341% 55/1,613,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.0317%	3,158
Remaining individualsnot grpmax-eligible	0.0144%	6,943
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
European (non-Finnish)	0.00178%	56,192
South Asian	0.0011%	91,082

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.Ser623=
Coding: c.1869C>T
MANE Select: NM_000226
dbSNP: rs749243428
Type: single nucleotide variant
Location: chr17:41567276 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 623: 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.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-ser623 (accessed [today's date]).

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