Is TRIOBP p.Trp1427Ter (c.4280G>A) pathogenic?

TRIOBP p.Trp1427Ter (c.4280G>A) is classified Likely pathogenic in TRIOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-23). Very rare (popmax 0.000172%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 28.

What condition is associated with TRIOBP p.Trp1427Ter (c.4280G>A)?

TRIOBP p.Trp1427Ter (c.4280G>A) is associated with autosomal recessive nonsyndromic hearing loss 28 (ClinVar).

How common is TRIOBP p.Trp1427Ter (c.4280G>A) in the general population?

TRIOBP p.Trp1427Ter (c.4280G>A) is very rare (popmax 0.000172%, nfe) (gnomAD).

TRIOBP p.Trp1427Ter

c.4280G>A · rs1329127252 · VCV1325234

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 28

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 9 of 24
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 0.98, phastCons 1
Overall
CADD	36.0	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

Grpmax group 0.000172% European (non-Finnish) · 2/1,165,232 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,583,540 alleles · very rare exomes 2/1,431,274 · genomes 0/152,266 · joint denominator

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: TRIOBP
Protein: p.Trp1427Ter
Coding: c.4280G>A
MANE Select: NM_001039141
dbSNP: rs1329127252
Type: single nucleotide variant
Location: chr22:37734616 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 40.77
Residue 1427: the 'disordered' region

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

Disease context

autosomal recessive nonsyndromic hearing loss 28 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRIOBP c.5184+1G>A Pathogenic/Likely pathogenic ★★ same condition
TRIOBP p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same condition
TRIOBP p.Arg1068Ter Pathogenic/Likely pathogenic ★★ same condition
TRIOBP p.Arg1117Ter Pathogenic ★★ same condition
TRIOBP p.Arg1745Ter Likely pathogenic ★★ same condition
TRIOBP p.Arg347Ter Pathogenic ★★ same condition
TRIOBP p.Arg399Ter Pathogenic/Likely pathogenic ★★ same condition
TRIOBP p.Arg448Ter 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/triobp-p-trp1427ter (accessed [today's date]).

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