Is TRAPPC9 p.Phe367Val (c.1099T>G) pathogenic?

TRAPPC9 p.Phe367Val (c.1099T>G) is classified Uncertain significance in TRAPPC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely pathogenic (0.8181); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal recessive 13.

What condition is associated with TRAPPC9 p.Phe367Val (c.1099T>G)?

TRAPPC9 p.Phe367Val (c.1099T>G) is associated with intellectual disability, autosomal recessive 13 (ClinVar).

How common is TRAPPC9 p.Phe367Val (c.1099T>G) in the general population?

TRAPPC9 p.Phe367Val (c.1099T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAPPC9 p.Phe367Val (c.1099T>G)?

AlphaMissense predicts likely pathogenic (score 0.8181) — an in-silico prediction, not a clinical call.

TRAPPC9 p.Phe367Val

c.1099T>G · rs2540230814 · VCV2671744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8181 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

intellectual disability, autosomal recessive 13

Computational evidence

Protein change
AlphaMissense	0.8181	likely pathogenic
REVEL	0.6	indeterminate
SaProt	LLR -10.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 160 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRAPPC9
Protein: p.Phe367Val
Coding: c.1099T>G
MANE Select: NM_001160372
dbSNP: rs2540230814
Type: single nucleotide variant
Location: chr8:140397655 (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

Disease context

intellectual disability, autosomal recessive 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAPPC9 c.2700-2A>T Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 c.3279+1G>A Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 p.Arg377Ter Pathogenic ★★ same condition
TRAPPC9 p.Arg472Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 p.Arg51Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 p.Arg614Ter Pathogenic ★★ same condition
TRAPPC9 p.Arg831Ter Pathogenic ★★ same condition
TRAPPC9 p.Glu123Ter Pathogenic ★★ same condition

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-phe367val (accessed [today's date]).

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