Is KRT14 p.Asp142Ala (c.425A>C) pathogenic?

KRT14 p.Asp142Ala (c.425A>C) is classified Uncertain significance in KRT14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.2586); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with KRT14 p.Asp142Ala (c.425A>C)?

KRT14 p.Asp142Ala (c.425A>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT14 p.Asp142Ala (c.425A>C) in the general population?

KRT14 p.Asp142Ala (c.425A>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about KRT14 p.Asp142Ala (c.425A>C)?

AlphaMissense predicts likely benign (score 0.2586) — an in-silico prediction, not a clinical call.

KRT14 p.Asp142Ala

c.425A>C · VCV4623219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2586	likely benign
REVEL	0.615	indeterminate
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 4,396 bp · p 3e-05 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,990 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000682% 11/1,613,836 alleles · ultra-rare exomes 6/1,461,746 · genomes 5/152,090 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
Remaining individualsnot grpmax-eligible	0.0048%	20,824
African / African-American	0.00134%	74,898
European (non-Finnish)	8.47e-05%	1,179,966

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: KRT14
Protein: p.Asp142Ala
Coding: c.425A>C
MANE Select: NM_000526
Type: single nucleotide variant
Location: chr17:41586410 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.00 · 6 PDB
Residue 142: the if rod domain; the 'coil 1a' region

Full KRT14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT14 p.Asp142Asn Uncertain significance ★ ⚠ same residue
KRT14 p.Arg407Trp Uncertain significance ★★ ⚠ same condition
KRT14 p.Arg41His Uncertain significance ★★ ⚠ same condition
KRT14 p.Arg449His Uncertain significance ★★ ⚠ same condition
KRT14 p.Arg469His Uncertain significance ★★ ⚠ same condition
KRT14 p.Gly27Ala Uncertain significance ★★ ⚠ same condition
KRT14 p.Gly47Arg Uncertain significance ★★ ⚠ same condition
KRT14 p.Ile400Ser Uncertain significance ★★ ⚠ 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/krt14-p-asp142ala (accessed [today's date]).

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