Is STUB1 p.Ala142Val (c.425C>T) pathogenic?

STUB1 p.Ala142Val (c.425C>T) is classified Uncertain significance in STUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely pathogenic (0.8932); Absent from gnomAD v4.1.

How common is STUB1 p.Ala142Val (c.425C>T) in the general population?

STUB1 p.Ala142Val (c.425C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STUB1 p.Ala142Val (c.425C>T)?

AlphaMissense predicts likely pathogenic (score 0.8932) — an in-silico prediction, not a clinical call.

STUB1 p.Ala142Val

c.425C>T · rs2543805295 · VCV2962135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8932	likely pathogenic
REVEL	0.236	benign-leaning
SaProt	LLR -12.57	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,960 bp · p 0.064 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: STUB1
Protein: p.Ala142Val
Coding: c.425C>T
MANE Select: NM_005861
dbSNP: rs2543805295
Type: single nucleotide variant
Location: chr16:681504 (GRCh38)
Gene constraint: LOEUF 1.294 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.84 · 27 PDB
Residue 142: an α-helix; the 'required for interaction with mapk7' region; the 'required for interaction with and ubiquitination of myocd' region

Full STUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STUB1 p.Asn65Ser Pathogenic/Likely pathogenic ★★ same type
STUB1 p.Tyr49Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
STUB1 p.Ala11Thr Uncertain significance ★★ ⚠ same type
STUB1 p.Arg173Leu Uncertain significance ★★ ⚠ same type
STUB1 p.Arg35Pro Uncertain significance ★★ ⚠ same type
STUB1 p.Asn34Ser Uncertain significance ★★ ⚠ same type
STUB1 p.Cys48Tyr Uncertain significance ★★ ⚠ same type
STUB1 p.Glu174Gly 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/stub1-p-ala142val (accessed [today's date]).

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