Is TRAPPC9 p.Val722= (c.2166A>G) pathogenic?

TRAPPC9 p.Val722= (c.2166A>G) is classified Likely benign in TRAPPC9 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-11-28). Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC9 p.Val722= (c.2166A>G)?

TRAPPC9 p.Val722= (c.2166A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC9 p.Val722= (c.2166A>G) in the general population?

TRAPPC9 p.Val722= (c.2166A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

TRAPPC9 p.Val722=

c.2166A>G · rs1386517290 · VCV1791622

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.05	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.35	GERP -0.7, phastCons 0.99
Overall
CADD	9.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000806% 13/1,613,436 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.000678%	147,420

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.Val722=
Coding: c.2166A>G
MANE Select: NM_001160372
dbSNP: rs1386517290
Type: single nucleotide variant
Location: chr8:140275770 (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-val722 (accessed [today's date]).

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