Is TRAPPC9 p.Ser380Pro (c.1138T>C) pathogenic?

TRAPPC9 p.Ser380Pro (c.1138T>C) is classified Uncertain significance in TRAPPC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: ambiguous (0.36); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRAPPC9 p.Ser380Pro (c.1138T>C)?

TRAPPC9 p.Ser380Pro (c.1138T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC9 p.Ser380Pro (c.1138T>C) in the general population?

TRAPPC9 p.Ser380Pro (c.1138T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAPPC9 p.Ser380Pro (c.1138T>C)?

AlphaMissense predicts ambiguous (score 0.36) — an in-silico prediction, not a clinical call.

TRAPPC9 p.Ser380Pro

c.1138T>C · VCV3973083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.36 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.36	ambiguous
REVEL	0.491	indeterminate
SaProt	LLR -8.25	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 160 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	24.2	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

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.Ser380Pro
Coding: c.1138T>C
MANE Select: NM_001160372
Type: single nucleotide variant
Location: chr8:140371177 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAPPC9 p.Arg472Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 p.Glu123Ter Pathogenic ★★ same condition
TRAPPC9 p.Glu97Ter Pathogenic ★★ same condition
TRAPPC9 c.-212G>C Uncertain significance ★★ same condition
TRAPPC9 c.-4C>A Uncertain significance ★★ same condition
TRAPPC9 c.-69C>T Uncertain significance ★★ same condition
TRAPPC9 c.-74C>A Uncertain significance ★★ same condition
TRAPPC9 p.Ala1093Val Uncertain significance ★★ ⚠ 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-ser380pro (accessed [today's date]).

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