Is TRAPPC2 p.His137Pro (c.410A>C) pathogenic?

TRAPPC2 p.His137Pro (c.410A>C) is classified Uncertain significance in TRAPPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.9505); Absent from gnomAD v4.1.

How common is TRAPPC2 p.His137Pro (c.410A>C) in the general population?

TRAPPC2 p.His137Pro (c.410A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAPPC2 p.His137Pro (c.410A>C)?

AlphaMissense predicts likely pathogenic (score 0.9505) — an in-silico prediction, not a clinical call.

TRAPPC2 p.His137Pro

c.410A>C · rs1425842137 · VCV1520870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9505 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9505	likely pathogenic
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -16.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 5,553 bp · p 5.3e-08 · regional, not allelic
Overall
CADD	25.2	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: TRAPPC2
Protein: p.His137Pro
Coding: c.410A>C
MANE Select: NM_001011658
dbSNP: rs1425842137
Type: single nucleotide variant
Location: chrX:13714420 (GRCh38)
Structure: AlphaFold pLDDT 92.44

Full TRAPPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAPPC2 p.His137Arg Uncertain significance ★ ⚠ same residue
TRAPPC2 p.His137Tyr Uncertain significance ★ ⚠ same residue
TRAPPC2 p.Arg122Ter Pathogenic ★★ same type
TRAPPC2 c.*1436C>T Uncertain significance ★★ same type
TRAPPC2 c.*942G>T Uncertain significance ★★ same type
TRAPPC2 c.*1052T>C Benign ★★ same type
TRAPPC2 c.*1229C>T Likely benign ★★ same type
TRAPPC2 c.*1739C>G 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/trappc2-p-his137pro (accessed [today's date]).

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