Is TRIP4 p.Lys89Ter (c.265A>T) pathogenic?

TRIP4 p.Lys89Ter (c.265A>T) is classified Pathogenic in TRIP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). Absent from gnomAD v4.1; Associated with spinal muscular atrophy with congenital bone fractures 1.

What condition is associated with TRIP4 p.Lys89Ter (c.265A>T)?

TRIP4 p.Lys89Ter (c.265A>T) is associated with spinal muscular atrophy with congenital bone fractures 1 (ClinVar).

How common is TRIP4 p.Lys89Ter (c.265A>T) in the general population?

TRIP4 p.Lys89Ter (c.265A>T) is absent from gnomAD v4.1 (gnomAD).

TRIP4 p.Lys89Ter

Q: How is Prenatal-onset spinal muscular atrophy with congenital bone fractures inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.265A>T · rs2505403454 · VCV1801722

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

spinal muscular atrophy with congenital bone fractures 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: TRIP4
Protein: p.Lys89Ter
Coding: c.265A>T
MANE Select: NM_016213
dbSNP: rs2505403454
Type: single nucleotide variant
Location: chr15:64394109 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.54 · 10 PDB

Full TRIP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinal muscular atrophy with congenital bone fractures 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Prenatal-onset spinal muscular atrophy with congenital bone fractures (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

TRIP4 p.Lys89Gln Uncertain significance ★ ⚠ same residue
TRIP4 p.Lys89= Likely benign ★ same residue
TRIP4 p.Arg309Ter Pathogenic/Likely pathogenic ★★ same condition
TRIP4 p.Trp297Ter Pathogenic ★★ same condition
TRIP4 p.Cys171Tyr Uncertain significance ★★ ⚠ same condition
TRIP4 c.1044-25G>A Benign ★★ same condition
TRIP4 p.Thr327= Benign/Likely benign ★★ same condition
TRIP4 c.1484-2A>G 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/trip4-p-lys89ter (accessed [today's date]).

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