Is TRIB2 p.Ser210Phe (c.629C>T) pathogenic?

TRIB2 p.Ser210Phe (c.629C>T) is classified Uncertain significance in TRIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: ambiguous (0.3698); Very rare (popmax 0.00153%, nfe).

How common is TRIB2 p.Ser210Phe (c.629C>T) in the general population?

TRIB2 p.Ser210Phe (c.629C>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about TRIB2 p.Ser210Phe (c.629C>T)?

AlphaMissense predicts ambiguous (score 0.3698) — an in-silico prediction, not a clinical call.

TRIB2 p.Ser210Phe

c.629C>T · VCV3461094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3698	ambiguous
REVEL	0.439	indeterminate
SaProt	LLR -7.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.92, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 22 kb · p 2.6e-07 · regional, not allelic
Overall
CADD	28.7	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

Grpmax group 0.00153% European (non-Finnish) · 18/1,180,040 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00118% 19/1,614,050 alleles · very rare exomes 16/1,461,888 · genomes 3/152,162 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00153%	65,558
South Asian	0.0011%	91,084

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: TRIB2
Protein: p.Ser210Phe
Coding: c.629C>T
MANE Select: NM_021643
Type: single nucleotide variant
Location: chr2:12740391 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.93 · 1 PDB
Residue 210: the protein kinase domain

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-ser210phe (accessed [today's date]).

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