Is TRIP12 p.Ala487Val (c.1460C>T) pathogenic?

TRIP12 p.Ala487Val (c.1460C>T) is classified Uncertain significance in TRIP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-05). AlphaMissense: likely pathogenic (0.6422); Absent from gnomAD v4.1.

How common is TRIP12 p.Ala487Val (c.1460C>T) in the general population?

TRIP12 p.Ala487Val (c.1460C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRIP12 p.Ala487Val (c.1460C>T)?

AlphaMissense predicts likely pathogenic (score 0.6422) — an in-silico prediction, not a clinical call.

TRIP12 p.Ala487Val

c.1460C>T · VCV4960433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6422 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6422	likely pathogenic
REVEL	0.298	indeterminate
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 40 kb · p 7.7e-07 · regional, not allelic
Overall
CADD	27.6	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 A439V vs ClinVar A487V) — 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: TRIP12
Protein: p.Ala487Val
Coding: c.1460C>T
MANE Select: NM_001348323
Type: single nucleotide variant
Location: chr2:229818503 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.06 · 5 PDB
Residue 439 UniProt numbering: the 'disordered' region; a UniProt-annotated variant site (in clabars; uncertain significance)

Full TRIP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIP12 c.3624+1G>A Likely pathogenic ★★ same type
TRIP12 p.Arg1635Gln Pathogenic/Likely pathogenic ★★ same type
TRIP12 p.Arg1635Ter Pathogenic/Likely pathogenic ★★ same type
TRIP12 p.Arg551Ter Pathogenic ★★ same type
TRIP12 p.Gln338Ter Pathogenic ★★ same type
TRIP12 p.Gln689Ter Pathogenic ★★ same type
TRIP12 c.4215+4A>G Uncertain significance ★★ same type
TRIP12 p.Ala1042Val 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/trip12-p-ala487val (accessed [today's date]).

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