Is KRT4 p.Pro102= (c.306C>T) pathogenic?

KRT4 p.Pro102= (c.306C>T) is classified Benign/Likely benign in KRT4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Rare (popmax 0.15%, mid); Associated with white sponge nevus 1.

What condition is associated with KRT4 p.Pro102= (c.306C>T)?

KRT4 p.Pro102= (c.306C>T) is associated with white sponge nevus 1 (ClinVar).

How common is KRT4 p.Pro102= (c.306C>T) in the general population?

KRT4 p.Pro102= (c.306C>T) is rare (popmax 0.15%, mid) (gnomAD).

How is White sponge nevus inherited?

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

KRT4 p.Pro102=

c.306C>T · rs373594963 · VCV309704

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.15%, mid)

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 -14	GERP -3.8
Overall
CADD	0.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.15% Middle Eastern · 4/2,662 alleles

Filtering AF 0.0512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0309%

Overall 0.0134% 135/1,010,816 alleles · rare exomes 126/1,002,612 · genomes 9/8,204 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.15%	665
Remaining individualsnot grpmax-eligible	0.0348%	2,870
South Asian	0.0282%	3,542
East Asian	0.023%	4,347
African / African-American	0.0184%	5,432
Admixed American	0.015%	6,662
European (non-Finnish)	0.0114%	8,801
Ashkenazi Jewishnot grpmax-eligible	0.00774%	12,916

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.Pro102=
Coding: c.306C>T
MANE Select: NM_002272
dbSNP: rs373594963
Type: single nucleotide variant
Location: chr12:52813753 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 102: 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-pro102 (accessed [today's date]).

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