Is TRAPPC2 p.Leu46= (c.138C>T) pathogenic?

TRAPPC2 p.Leu46= (c.138C>T) is classified Benign in TRAPPC2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-06). Ultra-rare (popmax 0.0229%, sas).

How common is TRAPPC2 p.Leu46= (c.138C>T) in the general population?

TRAPPC2 p.Leu46= (c.138C>T) is ultra-rare (popmax 0.0229%, sas) (gnomAD).

TRAPPC2 p.Leu46=

c.138C>T · rs1291714037 · VCV2191074

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.9	GERP -4.9
Overall
CADD	6.357	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0229% South Asian · 13/56,820 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00306% 37/1,210,188 alleles · ultra-rare exomes 35/1,097,633 · genomes 2/112,555 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0229%	4,371
Remaining individualsnot grpmax-eligible	0.0042%	23,792
European (non-Finnish)	0.00246%	40,682

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: TRAPPC2
Protein: p.Leu46=
Coding: c.138C>T
MANE Select: NM_001011658
dbSNP: rs1291714037
Type: single nucleotide variant
Location: chrX:13716634 (GRCh38)

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

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-leu46 (accessed [today's date]).

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