Is TAB2 p.Val28Ile (c.82G>A) pathogenic?

TAB2 p.Val28Ile (c.82G>A) is classified Uncertain significance in TAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-15). AlphaMissense: ambiguous (0.4212); Very rare (popmax 0.000254%, nfe).

How common is TAB2 p.Val28Ile (c.82G>A) in the general population?

TAB2 p.Val28Ile (c.82G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about TAB2 p.Val28Ile (c.82G>A)?

AlphaMissense predicts ambiguous (score 0.4212) — an in-silico prediction, not a clinical call.

TAB2 p.Val28Ile

c.82G>A · rs2483348448 · VCV1710651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4212 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4212	ambiguous
REVEL	0.533	indeterminate
SaProt	LLR -5.27	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 8,033 bp · p 4.3e-05 · regional, not allelic
Overall
CADD	27.8	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 0.000254% European (non-Finnish) · 3/1,179,884 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,968 alleles · very rare exomes 3/1,461,654 · genomes 0/152,314 · joint denominator

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.Val28Ile
Coding: c.82G>A
MANE Select: NM_001292034
dbSNP: rs2483348448
Type: single nucleotide variant
Location: chr6:149370079 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 53.24 · 6 PDB
Residue 28: the cue domain; an α-helix

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-val28ile (accessed [today's date]).

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