Is TRAPPC12 p.Pro19Ser (c.55C>T) pathogenic?

TRAPPC12 p.Pro19Ser (c.55C>T) is classified Uncertain significance in TRAPPC12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-04). AlphaMissense: likely benign (0.0622); Very rare (popmax 0.00409%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC12 p.Pro19Ser (c.55C>T)?

TRAPPC12 p.Pro19Ser (c.55C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC12 p.Pro19Ser (c.55C>T) in the general population?

TRAPPC12 p.Pro19Ser (c.55C>T) is very rare (popmax 0.00409%, afr) (gnomAD).

What do computational predictors say about TRAPPC12 p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

TRAPPC12 p.Pro19Ser

c.55C>T · rs752393610 · VCV2236089

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00409%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.13	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 -9.9	GERP -4.2
Regional constraint	o/e 1.08	unconstrained · MANE · 92 kb · p 0.008 · regional, not allelic
Overall
CADD	0.008	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

Grpmax group 0.00409% African / African-American · 3/73,362 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000501%

Overall 0.000356% 5/1,406,314 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00409%	24,454
Admixed American	0.00193%	51,934
European (non-Finnish)	8.68e-05%	1,151,454

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.Pro19Ser
Coding: c.55C>T
MANE Select: NM_016030
dbSNP: rs752393610
Type: single nucleotide variant
Location: chr2:3387678 (GRCh38)
Gene constraint: LOEUF 1.192 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52
Residue 19: 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.Pro19Thr Uncertain significance ★ ⚠ same residue
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

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-pro19ser (accessed [today's date]).

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