Is TRIB2 p.Ser95Arg (c.283A>C) pathogenic?

TRIB2 p.Ser95Arg (c.283A>C) is classified Uncertain significance in TRIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.1469); Absent from gnomAD v4.1.

How common is TRIB2 p.Ser95Arg (c.283A>C) in the general population?

TRIB2 p.Ser95Arg (c.283A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRIB2 p.Ser95Arg (c.283A>C)?

AlphaMissense predicts likely benign (score 0.1469) — an in-silico prediction, not a clinical call.

TRIB2 p.Ser95Arg

c.283A>C · VCV4190302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1469 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1469	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -8.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.6, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 22 kb · p 2.6e-07 · regional, not allelic
Overall
CADD	17.86	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: TRIB2
Protein: p.Ser95Arg
Coding: c.283A>C
MANE Select: NM_021643
Type: single nucleotide variant
Location: chr2:12723272 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.93 · 1 PDB
Residue 95: the protein kinase domain; a turn

Full TRIB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIB2 c.563+10A>T Benign ★★ same type
TRIB2 p.Ala102Ser Uncertain significance ★ ⚠ same type
TRIB2 p.Ala109Asp Uncertain significance ★ ⚠ same type
TRIB2 p.Ala160Thr Uncertain significance ★ ⚠ same type
TRIB2 p.Arg13Lys Uncertain significance ★ ⚠ same type
TRIB2 p.Arg18Leu Uncertain significance ★ same type
TRIB2 p.Arg203Gln Uncertain significance ★ ⚠ same type
TRIB2 p.Arg203Trp Uncertain significance ★ ⚠ same type

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/trib2-p-ser95arg (accessed [today's date]).

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