Is TRAPPC9 p.Pro637= (c.1911G>A) pathogenic?

TRAPPC9 p.Pro637= (c.1911G>A) is classified Conflicting classifications of pathogenicity in TRAPPC9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-27). Ultra-rare (popmax 0.0213%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC9 p.Pro637= (c.1911G>A)?

TRAPPC9 p.Pro637= (c.1911G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC9 p.Pro637= (c.1911G>A) in the general population?

TRAPPC9 p.Pro637= (c.1911G>A) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

TRAPPC9 p.Pro637=

c.1911G>A · rs148353187 · VCV1575157

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	Δ0.54	acceptor gain · deltas
Pangolin	Δ0.50	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -11	GERP -3.3
Overall
CADD	15.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/75,042 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00812% 131/1,614,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.179%	559
African / African-Americangrpmax	0.0213%	4,690
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	0.00432%	23,138
South Asian	0.00329%	30,360
Admixed American	0.00167%	60,016

Ashkenazi Jewish 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: TRAPPC9
Protein: p.Pro637=
Coding: c.1911G>A
MANE Select: NM_001160372
dbSNP: rs148353187
Type: single nucleotide variant
Location: chr8:140287678 (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.Pro637Leu Uncertain significance ★ ⚠ same residue
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

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-pro637 (accessed [today's date]).

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