Is TRIOBP p.Pro276Ser (c.826C>T) pathogenic?

TRIOBP p.Pro276Ser (c.826C>T) is classified Likely pathogenic in TRIOBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-26). AlphaMissense: likely benign (0.0804); Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 28.

What condition is associated with TRIOBP p.Pro276Ser (c.826C>T)?

TRIOBP p.Pro276Ser (c.826C>T) is associated with autosomal recessive nonsyndromic hearing loss 28 (ClinVar).

How common is TRIOBP p.Pro276Ser (c.826C>T) in the general population?

TRIOBP p.Pro276Ser (c.826C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRIOBP p.Pro276Ser (c.826C>T)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

TRIOBP p.Pro276Ser

c.826C>T · rs1569040134 · VCV627488

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 28

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign ⚠ discordant with ClinVar
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1	GERP -3
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.92 · regional, not allelic
Overall
CADD	0.669	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: TRIOBP
Protein: p.Pro276Ser
Coding: c.826C>T
MANE Select: NM_001039141
dbSNP: rs1569040134
Type: single nucleotide variant
Location: chr22:37723382 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 40.77
Residue 276: 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-pro276ser (accessed [today's date]).

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