Is TRAPPC9 p.Arg285Trp (c.853C>T) pathogenic?

TRAPPC9 p.Arg285Trp (c.853C>T) is classified Uncertain significance in TRAPPC9 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2024-01-02). AlphaMissense: likely pathogenic (0.7691); Ultra-rare (popmax 0.0858%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC9 p.Arg285Trp (c.853C>T)?

TRAPPC9 p.Arg285Trp (c.853C>T) is associated with Inborn genetic diseases, intellectual disability, intellectual disability, autosomal recessive 13 (ClinVar).

How common is TRAPPC9 p.Arg285Trp (c.853C>T) in the general population?

TRAPPC9 p.Arg285Trp (c.853C>T) is ultra-rare (popmax 0.0858%, nfe) (gnomAD).

What do computational predictors say about TRAPPC9 p.Arg285Trp (c.853C>T)?

AlphaMissense predicts likely pathogenic (score 0.7691) — an in-silico prediction, not a clinical call.

TRAPPC9 p.Arg285Trp

c.853C>T · rs141441030 · VCV235340

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.7691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0858%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7691	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 160 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0858% European (non-Finnish) · 1,012/1,180,030 alleles

Filtering AF 0.0813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0795%

Overall 0.0701% 1,132/1,614,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.098%	1,021
European (non-Finnish)grpmax	0.0858%	1,166
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Finnishnot grpmax-eligible	0.0219%	4,574
Admixed American	0.02%	5,002
South Asian	0.0176%	5,693
African / African-American	0.00933%	10,723

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.Arg285Trp
Coding: c.853C>T
MANE Select: NM_001160372
dbSNP: rs141441030
Type: single nucleotide variant
Location: chr8:140435118 (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

Also linked: intellectual disability intellectual disability, autosomal recessive 13

Similar variants

TRAPPC9 p.Arg285Gln Uncertain significance ★ ⚠ same residue
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

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-arg285trp (accessed [today's date]).

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