Is TRIOBP p.Arg792fs (c.2375_2379del) pathogenic?

TRIOBP p.Arg792fs (c.23752379del) is classified Likely pathogenic in TRIOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). Very rare (popmax 8.47e-05%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 28.

What condition is associated with TRIOBP p.Arg792fs (c.2375_2379del)?

TRIOBP p.Arg792fs (c.2375_2379del) is associated with autosomal recessive nonsyndromic hearing loss 28 (ClinVar).

How common is TRIOBP p.Arg792fs (c.2375_2379del) in the general population?

TRIOBP p.Arg792fs (c.2375_2379del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TRIOBP p.Arg792fs

c.2375_2379del · VCV4852230

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP 1.5
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	AACCCCAGAACATCCTGTGCCCAGCGGGACAATCCCAGAGCCTCCTCTCCCAATAGAGCTACACGAGACAACCCCAGAACATCCTGTGCCCAGCGGGACAATCCCAGAGCCTCCAGAACCTCCTCTCCCAATAGAGCCACACGAGAC simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,986 alleles

Overall 0.000186% 3/1,613,790 alleles · very rare exomes 2/1,461,790 · genomes 1/152,000 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
European (non-Finnish)grpmax	8.47e-05%	1,179,986

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg792fs
Coding: c.2375_2379del
MANE Select: NM_001039141
Type: Deletion
Location: chr22:37724929 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 40.77
Residue 792: 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 p.His1440fs Pathogenic/Likely pathogenic ★★ same condition
TRIOBP p.Ser578fs Pathogenic/Likely pathogenic ★★ same condition
TRIOBP p.Ser688_Pro711del Uncertain significance ★★ same condition
TRIOBP p.Gln398del Benign/Likely benign ★★ same condition
TRIOBP p.Ala619fs Likely pathogenic ★ same condition
TRIOBP p.Gln740fs Pathogenic ★ same condition
TRIOBP p.Leu1004fs Pathogenic ★ same condition
TRIOBP p.Phe368fs 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-arg792fs (accessed [today's date]).

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