Is TRAPPC9 p.Ala133= (c.399T>C) pathogenic?

TRAPPC9 p.Ala133= (c.399T>C) is classified Benign/Likely benign in TRAPPC9 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with TRAPPC9 p.Ala133= (c.399T>C)?

TRAPPC9 p.Ala133= (c.399T>C) is associated with Inborn genetic diseases (ClinVar).

TRAPPC9 p.Ala133=

Q: How common is TRAPPC9 p.Ala133= (c.399T>C) in the general population?

TRAPPC9 p.Ala133= (c.399T>C) is common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.399T>C · rs61739560 · VCV130638

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.7, phastCons 1
Overall
CADD	12.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11% African / African-American · 8,224/75,022 alleles

Filtering AF 10.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.7%

Overall 8.04% 129,798/1,614,090 alleles · common exomes 116,724/1,461,860 · genomes 13,074/152,230 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	15.2%	7
Amishnot grpmax-eligible	12.4%	8
African / African-Americangrpmax	11%	9
Middle Eastern	8.64%	12
European (non-Finnish)	8.47%	12
Remaining individualsnot grpmax-eligible	8.18%	12
Finnishnot grpmax-eligible	5.37%	19
Admixed American	5.24%	19
South Asian	5.16%	19
East Asian	0.294%	340

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.Ala133=
Coding: c.399T>C
MANE Select: NM_001160372
dbSNP: rs61739560
Type: single nucleotide variant
Location: chr8:140450975 (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-ala133 (accessed [today's date]).

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