Is TRAPPC2 p.Leu37= (c.111G>A) pathogenic?

TRAPPC2 p.Leu37= (c.111G>A) is classified Benign in TRAPPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-09). Very rare (popmax 0.00681%, nfe).

How common is TRAPPC2 p.Leu37= (c.111G>A) in the general population?

TRAPPC2 p.Leu37= (c.111G>A) is very rare (popmax 0.00681%, nfe) (gnomAD).

TRAPPC2 p.Leu37=

c.111G>A · rs376156270 · VCV1640603

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00681%, nfe)

⚠ 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 1.4	GERP 0.59, phastCons 1
Overall
CADD	12.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00681% European (non-Finnish) · 61/895,204 alleles

Filtering AF 0.0054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00587% 71/1,210,360 alleles · very rare exomes 56/1,097,808 · genomes 15/112,552 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0171%	5,832
European (non-Finnish)grpmax	0.00681%	14,675
Remaining individualsnot grpmax-eligible	0.0042%	23,790

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu37=
Coding: c.111G>A
MANE Select: NM_001011658
dbSNP: rs376156270
Type: single nucleotide variant
Location: chrX:13716661 (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-leu37 (accessed [today's date]).

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