Is KRT4 p.Asp240= (c.720C>T) pathogenic?

KRT4 p.Asp240= (c.720C>T) is classified Likely benign in KRT4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-20). Ultra-rare (popmax 0.016%, afr); Associated with KRT4-related disorder.

What condition is associated with KRT4 p.Asp240= (c.720C>T)?

KRT4 p.Asp240= (c.720C>T) is associated with KRT4-related disorder (ClinVar).

How common is KRT4 p.Asp240= (c.720C>T) in the general population?

KRT4 p.Asp240= (c.720C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

KRT4 p.Asp240=

c.720C>T · rs371875636 · VCV3033342

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

KRT4-related disorder

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 1.9	GERP -3.2, phastCons 1
Overall
CADD	7.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,924 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000867% 14/1,614,028 alleles · ultra-rare exomes 4/1,461,836 · genomes 10/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,244
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	8.47e-05%	1,180,008

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.Asp240=
Coding: c.720C>T
MANE Select: NM_002272
dbSNP: rs371875636
Type: single nucleotide variant
Location: chr12:52810774 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 240: the if rod domain; the 'coil 1b' region

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

Disease context

KRT4-related disorder

Similar variants

KRT4 p.Asp240Asn Uncertain significance ★ ⚠ same residue
KRT4 p.Gly477Val Uncertain significance ⚠ same condition
KRT4 p.Ala106Gly Uncertain significance ★★ ⚠ same type
KRT4 p.Asp153Asn Uncertain significance ★★ ⚠ same type
KRT4 p.Asp247Glu Uncertain significance ★★ same type
KRT4 c.1126-32G>A Benign ★★ same type
KRT4 c.1346+15A>G Benign ★★ same type
KRT4 c.1346+15A>T Likely benign ★★ same type

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-asp240 (accessed [today's date]).

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