Is TRAPPC9 p.Val1007Ile (c.3019G>A) pathogenic?

TRAPPC9 p.Val1007Ile (c.3019G>A) is classified Uncertain significance in TRAPPC9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-09). AlphaMissense: likely benign (0.0933); Ultra-rare (popmax 0.0323%, afr).

How common is TRAPPC9 p.Val1007Ile (c.3019G>A) in the general population?

TRAPPC9 p.Val1007Ile (c.3019G>A) is ultra-rare (popmax 0.0323%, afr) (gnomAD).

What do computational predictors say about TRAPPC9 p.Val1007Ile (c.3019G>A)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

TRAPPC9 p.Val1007Ile

c.3019G>A · rs368090693 · VCV1327899

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0323%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -7.40	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 1.3	GERP 1.6, phastCons 0.75
Regional constraint	o/e 0.94	unconstrained · MANE · 557 kb · p 0.13 · regional, not allelic
Overall
CADD	17.52	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 0.0323% African / African-American · 24/74,274 alleles

Filtering AF 0.0222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.00299% 47/1,572,262 alleles · ultra-rare exomes 37/1,419,918 · genomes 10/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0323%	3,095
East Asian	0.00933%	10,717
Remaining individualsnot grpmax-eligible	0.00328%	30,458
Admixed American	0.00184%	54,470
European (non-Finnish)	0.0013%	77,211
South Asian	0.00117%	85,358

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: TRAPPC9
Protein: p.Val1007Ile
Coding: c.3019G>A
MANE Select: NM_001160372
dbSNP: rs368090693
Type: single nucleotide variant
Location: chr8:139885915 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.98

Full TRAPPC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAPPC9 c.2700-2A>T Pathogenic/Likely pathogenic ★★ same type
TRAPPC9 c.2811-1G>A Likely pathogenic ★★ same type
TRAPPC9 c.3279+1G>A Pathogenic/Likely pathogenic ★★ same type
TRAPPC9 c.-204C>T Pathogenic/Likely pathogenic ★★ same type
TRAPPC9 p.Arg377Ter Pathogenic ★★ same type
TRAPPC9 p.Arg472Ter Pathogenic/Likely pathogenic ★★ same type
TRAPPC9 p.Arg51Ter Pathogenic/Likely pathogenic ★★ same type
TRAPPC9 p.Arg614Ter Pathogenic ★★ 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/trappc9-p-val1007ile (accessed [today's date]).

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