Is KRT4 p.Ser473= (c.1419C>T) pathogenic?

KRT4 p.Ser473= (c.1419C>T) is classified Benign in KRT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Low-frequency (popmax 1.28%, sas); Associated with white sponge nevus 1.

What condition is associated with KRT4 p.Ser473= (c.1419C>T)?

KRT4 p.Ser473= (c.1419C>T) is associated with white sponge nevus 1 (ClinVar).

How common is KRT4 p.Ser473= (c.1419C>T) in the general population?

KRT4 p.Ser473= (c.1419C>T) is low-frequency (popmax 1.28%, sas) (gnomAD).

How is White sponge nevus inherited?

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

KRT4 p.Ser473=

c.1419C>T · rs534019513 · VCV309669

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, sas)

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 -3.8	GERP -3.8
Overall
CADD	2.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.28% South Asian · 1,165/91,082 alleles

Filtering AF 1.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 0.0823% 1,329/1,614,176 alleles · low-frequency exomes 1,247/1,461,886 · genomes 82/152,290 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.28%	78
Remaining individualsnot grpmax-eligible	0.08%	1,250
Middle Eastern	0.0495%	2,021
Admixed American	0.0117%	8,575
East Asian	0.00891%	11,222
African / African-American	0.008%	12,504
European (non-Finnish)	0.00788%	12,689
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Ser473=
Coding: c.1419C>T
MANE Select: NM_002272
dbSNP: rs534019513
Type: single nucleotide variant
Location: chr12:52807213 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 473: the 'tail' 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.Ser473Cys Uncertain significance ★ ⚠ same residue
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

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-ser473 (accessed [today's date]).

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