Is TRAPPC12 p.Ser247Arg (c.739A>C) pathogenic?

TRAPPC12 p.Ser247Arg (c.739A>C) is classified Uncertain significance in TRAPPC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely benign (0.1835); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRAPPC12 p.Ser247Arg (c.739A>C)?

TRAPPC12 p.Ser247Arg (c.739A>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC12 p.Ser247Arg (c.739A>C) in the general population?

TRAPPC12 p.Ser247Arg (c.739A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAPPC12 p.Ser247Arg (c.739A>C)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

TRAPPC12 p.Ser247Arg

c.739A>C · rs2528235348 · VCV3181976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.078, phastCons 0.003
Regional constraint	o/e 1.08	unconstrained · MANE · 92 kb · p 0.008 · regional, not allelic
Overall
CADD	9.352	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRAPPC12
Protein: p.Ser247Arg
Coding: c.739A>C
MANE Select: NM_016030
dbSNP: rs2528235348
Type: single nucleotide variant
Location: chr2:3388362 (GRCh38)
Gene constraint: LOEUF 1.192 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52
Residue 247: the 'disordered' region

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-ser247arg (accessed [today's date]).

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