Is TRAPPC2 p.Ile89Val (c.265A>G) pathogenic?

TRAPPC2 p.Ile89Val (c.265A>G) is classified Benign in TRAPPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0558); Ultra-rare (popmax 0.0359%, amr).

How common is TRAPPC2 p.Ile89Val (c.265A>G) in the general population?

TRAPPC2 p.Ile89Val (c.265A>G) is ultra-rare (popmax 0.0359%, amr) (gnomAD).

What do computational predictors say about TRAPPC2 p.Ile89Val (c.265A>G)?

AlphaMissense predicts likely benign (score 0.0558) — an in-silico prediction, not a clinical call.

TRAPPC2 p.Ile89Val

c.265A>G · rs770926535 · VCV1943130

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0558 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0359%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0558	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -4.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.7	GERP -4.8
Regional constraint	o/e 0.48	unconstrained · MANE · 5,553 bp · p 5.3e-08 · regional, not allelic
Overall
CADD	0.006	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 0.0359% Admixed American · 16/44,618 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0183%

Overall 0.00168% 20/1,191,723 alleles · ultra-rare exomes 19/1,078,761 · genomes 1/112,962 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0359%	2,789
European (non-Finnish)	0.000453%	220,693

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: TRAPPC2
Protein: p.Ile89Val
Coding: c.265A>G
MANE Select: NM_001011658
dbSNP: rs770926535
Type: single nucleotide variant
Location: chrX:13716063 (GRCh38)

Full TRAPPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/trappc2-p-ile89val (accessed [today's date]).

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