Is TRAPPC12 p.Phe227fs (c.678dup) pathogenic?

TRAPPC12 p.Phe227fs (c.678dup) is classified Pathogenic in TRAPPC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-03). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with TRAPPC12 p.Phe227fs (c.678dup)?

TRAPPC12 p.Phe227fs (c.678dup) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC12 p.Phe227fs (c.678dup) in the general population?

TRAPPC12 p.Phe227fs (c.678dup) is absent from gnomAD (gnomAD).

TRAPPC12 p.Phe227fs

c.678dup · rs2528233843 · VCV2340793

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRAPPC12
Protein: p.Phe227fs
Coding: c.678dup
MANE Select: NM_016030
dbSNP: rs2528233843
Type: Duplication
Location: chr2:3388299 (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.Phe227Cys Uncertain significance ★ ⚠ same residue
TRAPPC12 p.Phe227Ser Uncertain significance ★ ⚠ same residue
TRAPPC12 p.Phe227Leu Uncertain significance ★★ ⚠ same residue
TRAPPC12 p.Phe227= Benign ★★ 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

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-phe227fs (accessed [today's date]).

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