Is TRAPPC4 p.Ile3Val (c.7A>G) pathogenic?

TRAPPC4 p.Ile3Val (c.7A>G) is classified Uncertain significance in TRAPPC4 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-04). AlphaMissense: likely benign (0.1154); Very rare (popmax 0.00446%, eas).

How common is TRAPPC4 p.Ile3Val (c.7A>G) in the general population?

TRAPPC4 p.Ile3Val (c.7A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about TRAPPC4 p.Ile3Val (c.7A>G)?

AlphaMissense predicts likely benign (score 0.1154) — an in-silico prediction, not a clinical call.

TRAPPC4 p.Ile3Val

c.7A>G · rs781822453 · VCV2316119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1154 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1154	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -6.32	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,028 bp · p 0.78 · regional, not allelic
Overall
CADD	21.4	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 0.00446% East Asian · 2/44,814 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000434% 7/1,611,934 alleles · very rare exomes 6/1,459,846 · genomes 1/152,088 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,407
Admixed American	0.00167%	59,966
European (non-Finnish)	0.000339%	294,578

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: TRAPPC4
Protein: p.Ile3Val
Coding: c.7A>G
MANE Select: NM_016146
dbSNP: rs781822453
Type: single nucleotide variant
Location: chr11:119018802 (GRCh38)
Gene constraint: LOEUF 1.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.02 · 3 PDB
Residue 3: a β-strand

Full TRAPPC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAPPC4 c.454+3A>G Pathogenic/Likely pathogenic ★★ same type
TRAPPC4 c.176-31C>G Benign ★★ same type
TRAPPC4 c.176-40C>G Benign ★★ same type
TRAPPC4 c.176-43C>T Benign ★★ same type
TRAPPC4 c.350+129T>C Benign ★★ same type
TRAPPC4 c.350+58C>T Benign ★★ same type
TRAPPC4 c.351-58C>A Benign ★★ same type
TRAPPC4 c.454+225G>T Benign ★★ 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/trappc4-p-ile3val (accessed [today's date]).

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