Is KRT4 p.Lys96= (c.288G>A) pathogenic?

KRT4 p.Lys96= (c.288G>A) is classified Benign in KRT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Rare (popmax 0.193%, amr); Associated with white sponge nevus 1.

What condition is associated with KRT4 p.Lys96= (c.288G>A)?

KRT4 p.Lys96= (c.288G>A) is associated with white sponge nevus 1 (ClinVar).

How common is KRT4 p.Lys96= (c.288G>A) in the general population?

KRT4 p.Lys96= (c.288G>A) is rare (popmax 0.193%, amr) (gnomAD).

How is White sponge nevus inherited?

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

KRT4 p.Lys96=

c.288G>A · rs372013854 · VCV309705

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.193%, amr)

Conditions

white sponge nevus 1

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 -0.93	GERP -3.5
Overall
CADD	1.606	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.193% Admixed American · 12/6,202 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0874%

Overall 0.0834% 319/382,586 alleles · rare exomes 285/378,826 · genomes 34/3,760 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.193%	517
South Asian	0.139%	721
Middle Eastern	0.133%	751
European (non-Finnish)	0.0855%	1,169
African / African-American	0.0657%	1,522
Remaining individualsnot grpmax-eligible	0.0412%	2,427

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: KRT4
Protein: p.Lys96=
Coding: c.288G>A
MANE Select: NM_002272
dbSNP: rs372013854
Type: single nucleotide variant
Location: chr12:52813771 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 96: the 'head' region

Full KRT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

white sponge nevus 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For White sponge nevus (Orphanet):

Inheritance: Autosomal dominant

Similar variants

KRT4 p.Ala106Gly Uncertain significance ★★ ⚠ same condition
KRT4 p.Asp153Asn Uncertain significance ★★ ⚠ same condition
KRT4 p.Asp247Glu Uncertain significance ★★ same condition
KRT4 c.1346+15A>G Benign ★★ same condition
KRT4 c.1346+15A>T Likely benign ★★ same condition
KRT4 c.1381+15C>T Benign ★★ same condition
KRT4 c.678-14G>A Benign ★★ same condition
KRT4 c.678-3C>T 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/krt4-p-lys96 (accessed [today's date]).

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