Is TRAPPC9 p.Ala412Ser (c.1234G>T) pathogenic?

TRAPPC9 p.Ala412Ser (c.1234G>T) is classified Uncertain significance in TRAPPC9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-03-24). AlphaMissense: ambiguous (0.4944); Ultra-rare (popmax 0.0227%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC9 p.Ala412Ser (c.1234G>T)?

TRAPPC9 p.Ala412Ser (c.1234G>T) is associated with Inborn genetic diseases, intellectual disability, autosomal recessive 13 (ClinVar).

How common is TRAPPC9 p.Ala412Ser (c.1234G>T) in the general population?

TRAPPC9 p.Ala412Ser (c.1234G>T) is ultra-rare (popmax 0.0227%, nfe) (gnomAD).

What do computational predictors say about TRAPPC9 p.Ala412Ser (c.1234G>T)?

AlphaMissense predicts ambiguous (score 0.4944) — an in-silico prediction, not a clinical call.

TRAPPC9 p.Ala412Ser

c.1234G>T · rs201836353 · VCV1774562

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4944 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4944	ambiguous
REVEL	0.587	indeterminate
SaProt	LLR -9.54	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 160 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	27.0	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 0.0227% European (non-Finnish) · 268/1,180,054 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0195%

Overall 0.0175% 282/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0227%	4,403
African / African-American	0.0133%	7,494
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ala412Ser
Coding: c.1234G>T
MANE Select: NM_001160372
dbSNP: rs201836353
Type: single nucleotide variant
Location: chr8:140371081 (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, autosomal recessive 13

Similar variants

TRAPPC9 p.Ala412Thr Likely pathogenic ★ 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-ala412ser (accessed [today's date]).

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