Is KRT2 p.Asp288= (c.864C>T) pathogenic?

KRT2 p.Asp288= (c.864C>T) is classified Uncertain significance in KRT2 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-12). Very rare (popmax 0.00803%, afr); Associated with superficial epidermolytic ichthyosis.

What condition is associated with KRT2 p.Asp288= (c.864C>T)?

KRT2 p.Asp288= (c.864C>T) is associated with superficial epidermolytic ichthyosis (ClinVar).

How common is KRT2 p.Asp288= (c.864C>T) in the general population?

KRT2 p.Asp288= (c.864C>T) is very rare (popmax 0.00803%, afr) (gnomAD).

How is Superficial epidermolytic ichthyosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

KRT2 p.Asp288=

c.864C>T · rs765620105 · VCV309612

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00803%, afr)

Conditions

superficial epidermolytic ichthyosis

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 -6.6	GERP -3.7
Overall
CADD	0.172	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00803% African / African-American · 6/74,746 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00218% 35/1,606,274 alleles · very rare exomes 31/1,454,124 · genomes 4/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00803%	12,458
South Asian	0.0066%	15,152
East Asian	0.00223%	44,836
European (non-Finnish)	0.00179%	55,867
Remaining individualsnot grpmax-eligible	0.00161%	62,198

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: KRT2
Protein: p.Asp288=
Coding: c.864C>T
MANE Select: NM_000423
dbSNP: rs765620105
Type: single nucleotide variant
Location: chr12:52649100 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.38
Residue 288: the if rod domain; the 'coil 1b' region

Full KRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Superficial epidermolytic ichthyosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

KRT2 p.Glu487Lys Pathogenic ★★ same condition
KRT2 p.Glu488Lys Likely pathogenic ★★ same condition
KRT2 c.1249-4A>G Benign ★★ same condition
KRT2 c.1249-7G>T Benign ★★ same condition
KRT2 c.861+6C>G Benign/Likely benign ★★ same condition
KRT2 c.*215C>T Benign ★★ same condition
KRT2 c.*42T>C Benign ★★ same condition
KRT2 p.Ala427= Benign ★★ 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/krt2-p-asp288 (accessed [today's date]).

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