Is TRIP12 p.Pro134fs (c.399dup) pathogenic?

TRIP12 p.Pro134fs (c.399dup) is classified Pathogenic/Likely pathogenic in TRIP12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-01). No gnomAD frequency available for this variant; Associated with Clark-Baraitser syndrome.

What condition is associated with TRIP12 p.Pro134fs (c.399dup)?

TRIP12 p.Pro134fs (c.399dup) is associated with Clark-Baraitser syndrome (ClinVar).

How common is TRIP12 p.Pro134fs (c.399dup) in the general population?

TRIP12 p.Pro134fs (c.399dup) is no gnomAD frequency available for this variant (gnomAD).

TRIP12 p.Pro134fs

c.399dup · rs2060119917 · VCV997950

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Clark-Baraitser syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 42
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.7	GERP 2.5, 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: TRIP12
Protein: p.Pro134fs
Coding: c.399dup
MANE Select: NM_001348323
dbSNP: rs2060119917
Type: Duplication
Location: chr2:229859399 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.06 · 5 PDB
Residue 134: the 'disordered' region

Full TRIP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Clark-Baraitser syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRIP12 p.Ile1164fs Pathogenic ★★ same condition
TRIP12 p.Ala1821fs Pathogenic ★ same condition
TRIP12 p.Asn1457fs Pathogenic ★ same condition
TRIP12 p.Gly1069fs Pathogenic ★ same condition
TRIP12 p.His1811fs Likely pathogenic ★ same condition
TRIP12 p.Leu1071fs Pathogenic ★ same condition
TRIP12 p.Ser923Ter Likely pathogenic ★ same condition
TRIP12 p.Tyr2037Ter Likely 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/trip12-p-pro134fs (accessed [today's date]).

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