Is TRIP13 p.Ile432Val (c.1294A>G) pathogenic?

TRIP13 p.Ile432Val (c.1294A>G) is classified Likely benign in TRIP13 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0561); Rare (popmax 0.169%, eas).

How common is TRIP13 p.Ile432Val (c.1294A>G) in the general population?

TRIP13 p.Ile432Val (c.1294A>G) is rare (popmax 0.169%, eas) (gnomAD).

What do computational predictors say about TRIP13 p.Ile432Val (c.1294A>G)?

AlphaMissense predicts likely benign (score 0.0561) — an in-silico prediction, not a clinical call.

TRIP13 p.Ile432Val

c.1294A>G · rs200263887 · VCV735470

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0561 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0561	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -4.3
Regional constraint	o/e 0.73	unconstrained · MANE · 5,170 bp · p 0.0014 · regional, not allelic
Overall
CADD	0.005	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

Grpmax group 0.169% East Asian · 76/44,884 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.00867% 140/1,614,050 alleles · rare exomes 120/1,461,708 · genomes 20/152,342 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.169%	591
Remaining individualsnot grpmax-eligible	0.0352%	2,841
South Asian	0.0329%	3,035
Admixed American	0.00167%	60,012
African / African-American	0.00133%	75,040
European (non-Finnish)	0.000847%	118,000

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: TRIP13
Protein: p.Ile432Val
Coding: c.1294A>G
MANE Select: NM_004237
dbSNP: rs200263887
Type: single nucleotide variant
Location: chr5:917098 (GRCh38)
Gene constraint: LOEUF 0.592 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 6 PDB
Residue 432: a UniProt-annotated variant site (in mva3; loss of protein expression; impairment of spindle assembly checkpoint)

Full TRIP13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIP13 p.Ile432Leu Uncertain significance ★ ⚠ same residue
TRIP13 p.Ala92Glu Uncertain significance ★★ ⚠ same type
TRIP13 p.Arg28Ser Uncertain significance ★★ ⚠ same type
TRIP13 p.Arg347Cys Uncertain significance ★★ ⚠ same type
TRIP13 p.Asp238Asn Uncertain significance ★★ ⚠ same type
TRIP13 p.Ile330Val Uncertain significance ★★ ⚠ same type
TRIP13 p.Lys379Arg Uncertain significance ★★ ⚠ same type
TRIP13 p.Val307Met 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/trip13-p-ile432val (accessed [today's date]).

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