Is ITCH p.Asp314Val (c.941A>T) pathogenic?

ITCH p.Asp314Val (c.941A>T) is classified Uncertain significance in ITCH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.7388); Absent from gnomAD v4.1.

How common is ITCH p.Asp314Val (c.941A>T) in the general population?

ITCH p.Asp314Val (c.941A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITCH p.Asp314Val (c.941A>T)?

AlphaMissense predicts likely pathogenic (score 0.7388) — an in-silico prediction, not a clinical call.

ITCH p.Asp314Val

c.941A>T · VCV4542385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7388 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7388	likely pathogenic
REVEL	0.617	indeterminate
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 68 kb · p 1.5e-36 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D355V vs ClinVar D314V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITCH
Protein: p.Asp314Val
Coding: c.941A>T
MANE Select: NM_031483
Type: single nucleotide variant
Location: chr20:34442279 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.39 · 12 PDB

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

Similar variants

ITCH p.Asp314= Likely benign ★ same residue
ITCH c.1952+6T>C Uncertain significance ★★ same type
ITCH c.966-9C>G Uncertain significance ★★ same type
ITCH p.Arg192Ser Uncertain significance ★★ ⚠ same type
ITCH p.Arg217Gln Uncertain significance ★★ ⚠ same type
ITCH p.Arg224Cys Uncertain significance ★★ ⚠ same type
ITCH p.Arg763Ser Uncertain significance ★★ ⚠ same type
ITCH p.Arg82Gly Uncertain significance ★★ ⚠ 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/itch-p-asp314val (accessed [today's date]).

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