Is TRAPPC9 p.Phe486= (c.1458C>T) pathogenic?

TRAPPC9 p.Phe486= (c.1458C>T) is classified Benign/Likely benign in TRAPPC9 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.62%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC9 p.Phe486= (c.1458C>T)?

TRAPPC9 p.Phe486= (c.1458C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC9 p.Phe486= (c.1458C>T) in the general population?

TRAPPC9 p.Phe486= (c.1458C>T) is low-frequency (popmax 2.62%, afr) (gnomAD).

TRAPPC9 p.Phe486=

c.1458C>T · rs34179337 · VCV130621

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.62%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.074	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.36, phastCons 1
Overall
CADD	8.785	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.62% African / African-American · 1,966/75,014 alleles

Filtering AF 2.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.49%

Overall 0.177% 2,859/1,614,176 alleles · low-frequency exomes 1,669/1,461,890 · genomes 1,190/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.62%	38
East Asian	1.18%	85
Remaining individualsnot grpmax-eligible	0.24%	417
Admixed American	0.172%	583
Middle Eastern	0.099%	1,010
South Asian	0.0977%	1,023
European (non-Finnish)	0.00144%	69,415

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.Phe486=
Coding: c.1458C>T
MANE Select: NM_001160372
dbSNP: rs34179337
Type: single nucleotide variant
Location: chr8:140360087 (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-phe486 (accessed [today's date]).

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