Is TRAPPC2 p.Val49Ile (c.145G>A) pathogenic?

TRAPPC2 p.Val49Ile (c.145G>A) is classified Uncertain significance in TRAPPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-26). AlphaMissense: likely benign (0.1886); Very rare (popmax 0.000112%, nfe).

How common is TRAPPC2 p.Val49Ile (c.145G>A) in the general population?

TRAPPC2 p.Val49Ile (c.145G>A) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about TRAPPC2 p.Val49Ile (c.145G>A)?

AlphaMissense predicts likely benign (score 0.1886) — an in-silico prediction, not a clinical call.

TRAPPC2 p.Val49Ile

c.145G>A · VCV4765819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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	0.1886	likely benign
REVEL	0.531	indeterminate
SaProt	LLR -8.05	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 1.8	GERP 2.4, phastCons 0.93
Regional constraint	o/e 0.48	unconstrained · MANE · 5,553 bp · p 5.3e-08 · regional, not allelic
Overall
CADD	16.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,246 alleles

Overall 8.25e-05% 1/1,211,510 alleles · very rare exomes 1/1,097,689 · genomes 0/113,821 · joint denominator

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.Val49Ile
Coding: c.145G>A
MANE Select: NM_001011658
Type: single nucleotide variant
Location: chrX:13716627 (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-val49ile (accessed [today's date]).

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