Is KRT4 p.Phe89= (c.267T>C) pathogenic?

KRT4 p.Phe89= (c.267T>C) is classified Benign in KRT4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Common (popmax 6.02%, sas) — too common for a highly-penetrant pathogenic allele; Associated with white sponge nevus 1.

What condition is associated with KRT4 p.Phe89= (c.267T>C)?

KRT4 p.Phe89= (c.267T>C) is associated with white sponge nevus 1 (ClinVar).

How is White sponge nevus inherited?

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

KRT4 p.Phe89=

Q: How common is KRT4 p.Phe89= (c.267T>C) in the general population?

KRT4 p.Phe89= (c.267T>C) is common (popmax 6.02%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.267T>C · rs372168510 · VCV309706

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.02%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

white sponge nevus 1

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 -0.34	GERP -3.8
Overall
CADD	4.841	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.02% South Asian · 1,564/25,984 alleles

Filtering AF 5.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.67%

Overall 0.683% 1,821/266,440 alleles · common exomes 1,728/263,228 · genomes 93/3,212 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	6.02%	17
Middle Eastern	1.45%	69
Ashkenazi Jewishnot grpmax-eligible	0.718%	139
Remaining individualsnot grpmax-eligible	0.64%	156
African / African-American	0.0846%	1,182
European (non-Finnish)	0.0594%	1,683
Admixed American	0.0233%	4,297
Finnishnot grpmax-eligible	0.00715%	13,990

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.Phe89=
Coding: c.267T>C
MANE Select: NM_002272
dbSNP: rs372168510
Type: single nucleotide variant
Location: chr12:52813792 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 89: 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-phe89 (accessed [today's date]).

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