Is TRAPPC9 p.Phe96= (c.288T>C) pathogenic?

TRAPPC9 p.Phe96= (c.288T>C) is classified Benign in TRAPPC9 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 56.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, autosomal recessive 13.

What condition is associated with TRAPPC9 p.Phe96= (c.288T>C)?

TRAPPC9 p.Phe96= (c.288T>C) is associated with intellectual disability, autosomal recessive 13 (ClinVar).

TRAPPC9 p.Phe96=

Q: How common is TRAPPC9 p.Phe96= (c.288T>C) in the general population?

TRAPPC9 p.Phe96= (c.288T>C) is common (popmax 56.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.288T>C · rs3735802 · VCV130635

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 56.7%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, autosomal recessive 13

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 -5.2	GERP -3.2
Overall
CADD	0.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 56.7% European (non-Finnish) · 668,839/1,179,930 alleles

Filtering AF 56.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 56.5%

Overall 56% 903,845/1,613,678 alleles · common exomes 819,183/1,461,818 · genomes 84,662/151,860 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	60.9%	2
Finnishnot grpmax-eligible	59.8%	2
European (non-Finnish)grpmax	56.7%	2
Remaining individualsnot grpmax-eligible	55.8%	2
South Asian	55.6%	2
African / African-American	54.5%	2
Middle Eastern	54.2%	2
East Asian	53.2%	2
Amishnot grpmax-eligible	49.3%	2
Admixed American	41.5%	2

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.Phe96=
Coding: c.288T>C
MANE Select: NM_001160372
dbSNP: rs3735802
Type: single nucleotide variant
Location: chr8:140451086 (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

intellectual disability, autosomal recessive 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAPPC9 c.2700-2A>T Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 c.3279+1G>A Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 p.Arg377Ter Pathogenic ★★ same condition
TRAPPC9 p.Arg472Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 p.Arg51Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC9 p.Arg614Ter Pathogenic ★★ same condition
TRAPPC9 p.Arg831Ter Pathogenic ★★ same condition
TRAPPC9 p.Glu123Ter Pathogenic ★★ 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-phe96 (accessed [today's date]).

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