Is TRIOBP p.Asp1069fs (c.3202_3203del) pathogenic?

TRIOBP p.Asp1069fs (c.32023203del) is classified Pathogenic in TRIOBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-01-01). Very rare (popmax 0.0011%, sas); Associated with autosomal recessive nonsyndromic hearing loss 28.

What condition is associated with TRIOBP p.Asp1069fs (c.3202_3203del)?

TRIOBP p.Asp1069fs (c.3202_3203del) is associated with autosomal recessive nonsyndromic hearing loss 28 (ClinVar).

How common is TRIOBP p.Asp1069fs (c.3202_3203del) in the general population?

TRIOBP p.Asp1069fs (c.3202_3203del) is very rare (popmax 0.0011%, sas) (gnomAD).

TRIOBP p.Asp1069fs

c.3202_3203del · rs1601632909 · VCV1496

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 3	GERP 1.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,004 alleles

Overall 6.2e-05% 1/1,612,262 alleles · very rare exomes 1/1,460,342 · genomes 0/151,920 · 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.Asp1069fs
Coding: c.3202_3203del
MANE Select: NM_001039141
dbSNP: rs1601632909
Type: Deletion
Location: chr22:37725758 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 40.77
Residue 1069: 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.Arg792fs Likely pathogenic ★ same condition
TRIOBP p.Gln740fs Pathogenic ★ same condition
TRIOBP p.Leu1004fs 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-asp1069fs (accessed [today's date]).

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