Is TAB2 p.Pro130Ala (c.388C>G) pathogenic?

TAB2 p.Pro130Ala (c.388C>G) is classified Uncertain significance in TAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.0933); Ultra-rare (popmax 0.0117%, amr).

How common is TAB2 p.Pro130Ala (c.388C>G) in the general population?

TAB2 p.Pro130Ala (c.388C>G) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about TAB2 p.Pro130Ala (c.388C>G)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

TAB2 p.Pro130Ala

c.388C>G · rs755789570 · VCV1414562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.688	pathogenic-leaning
SaProt	LLR -6.87	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	22.6	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 0.0117% Admixed American · 7/60,012 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000558% 9/1,614,072 alleles · ultra-rare exomes 7/1,461,884 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
European (non-Finnish)	0.000169%	590,023

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: TAB2
Protein: p.Pro130Ala
Coding: c.388C>G
MANE Select: NM_001292034
dbSNP: rs755789570
Type: single nucleotide variant
Location: chr6:149378303 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 53.24 · 6 PDB
Residue 130: the 'disordered' region

Full TAB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TAB2 c.1604-2A>G Pathogenic/Likely pathogenic ★★ same type
TAB2 c.1764+1G>A Pathogenic/Likely pathogenic ★★ same type
TAB2 p.Arg546Ter Pathogenic/Likely pathogenic ★★ same type
TAB2 p.Arg574Ter Likely pathogenic ★★ same type
TAB2 p.Ala618Val Uncertain significance ★★ ⚠ same type
TAB2 p.Arg173Lys Uncertain significance ★★ ⚠ same type
TAB2 p.Arg17Gln Uncertain significance ★★ ⚠ same type
TAB2 p.Arg576Cys 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/tab2-p-pro130ala (accessed [today's date]).

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