Is TRAPPC12 p.Arg641Ser (c.1923G>T) pathogenic?

TRAPPC12 p.Arg641Ser (c.1923G>T) is classified Uncertain significance in TRAPPC12 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-09). AlphaMissense: ambiguous (0.4321); Very rare (popmax 0.00991%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC12 p.Arg641Ser (c.1923G>T)?

TRAPPC12 p.Arg641Ser (c.1923G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC12 p.Arg641Ser (c.1923G>T) in the general population?

TRAPPC12 p.Arg641Ser (c.1923G>T) is very rare (popmax 0.00991%, nfe) (gnomAD).

What do computational predictors say about TRAPPC12 p.Arg641Ser (c.1923G>T)?

AlphaMissense predicts ambiguous (score 0.4321) — an in-silico prediction, not a clinical call.

TRAPPC12 p.Arg641Ser

c.1923G>T · rs145629807 · VCV2347044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00991%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4321	ambiguous
REVEL	0.332	indeterminate
SaProt	LLR -6.78	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.1
Regional constraint	o/e 1.08	unconstrained · MANE · 92 kb · p 0.008 · regional, not allelic
Overall
CADD	0.654	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 0.00991% European (non-Finnish) · 117/1,180,050 alleles

Filtering AF 0.00842% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.00762% 123/1,614,066 alleles · very rare exomes 115/1,461,840 · genomes 8/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00991%	10,086
Remaining individualsnot grpmax-eligible	0.0064%	15,621
African / African-American	0.00267%	37,471

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: TRAPPC12
Protein: p.Arg641Ser
Coding: c.1923G>T
MANE Select: NM_016030
dbSNP: rs145629807
Type: single nucleotide variant
Location: chr2:3478891 (GRCh38)
Gene constraint: LOEUF 1.192 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52

Full TRAPPC12 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

TRAPPC12 p.Ala309Val Uncertain significance ★★ ⚠ same condition
TRAPPC12 p.Ala485Thr Uncertain significance ★★ ⚠ same condition
TRAPPC12 p.Ala637Val Uncertain significance ★★ ⚠ same condition
TRAPPC12 p.Arg533Gly Uncertain significance ★★ same condition
TRAPPC12 p.Arg543Cys Uncertain significance ★★ ⚠ same condition
TRAPPC12 p.Asp212Glu Uncertain significance ★★ ⚠ same condition
TRAPPC12 p.Asp212Tyr Uncertain significance ★★ same condition
TRAPPC12 p.Asp375Glu 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/trappc12-p-arg641ser (accessed [today's date]).

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