Is TRIOBP p.Arg595Ter (c.1783C>T) pathogenic?

TRIOBP p.Arg595Ter (c.1783C>T) is classified Pathogenic in TRIOBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-13). Very rare (popmax 0.00173%, amr); Associated with autosomal recessive nonsyndromic hearing loss 28.

What condition is associated with TRIOBP p.Arg595Ter (c.1783C>T)?

TRIOBP p.Arg595Ter (c.1783C>T) is associated with autosomal recessive nonsyndromic hearing loss 28 (ClinVar).

How common is TRIOBP p.Arg595Ter (c.1783C>T) in the general population?

TRIOBP p.Arg595Ter (c.1783C>T) is very rare (popmax 0.00173%, amr) (gnomAD).

TRIOBP p.Arg595Ter

c.1783C>T · rs371412957 · VCV2445671

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00173%, amr)

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 7 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -0.26
Overall
CADD	23.4	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 0.00173% Admixed American · 1/57,658 alleles

Overall 0.000252% 4/1,584,876 alleles · very rare exomes 4/1,461,594 · genomes 0/123,282 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00173%	57,658
African / African-American	0.00163%	61,270
South Asian	0.00112%	89,670
European (non-Finnish)	8.53e-05%	1,172,005

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.Arg595Ter
Coding: c.1783C>T
MANE Select: NM_001039141
dbSNP: rs371412957
Type: single nucleotide variant
Location: chr22:37724339 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 40.77
Residue 595: 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-arg595ter (accessed [today's date]).

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