Is TAB2 p.Ala627Thr (c.1879G>A) pathogenic?

TAB2 p.Ala627Thr (c.1879G>A) is classified Uncertain significance in TAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-16). AlphaMissense: ambiguous (0.5083); Very rare (popmax 0.00223%, eas).

How common is TAB2 p.Ala627Thr (c.1879G>A) in the general population?

TAB2 p.Ala627Thr (c.1879G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about TAB2 p.Ala627Thr (c.1879G>A)?

AlphaMissense predicts ambiguous (score 0.5083) — an in-silico prediction, not a clinical call.

TAB2 p.Ala627Thr

c.1879G>A · rs775340413 · VCV1944385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.5083	ambiguous
REVEL	0.313	indeterminate
SaProt	LLR -5.96	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 0.43	unconstrained · MANE · 12 kb · p 7.4e-11 · regional, not allelic
Overall
CADD	26.8	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 0.00223% East Asian · 1/44,788 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,613,168 alleles · very rare exomes 18/1,461,200 · genomes 1/151,968 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,788
Remaining individualsnot grpmax-eligible	0.0016%	62,434
European (non-Finnish)	0.00136%	73,722
South Asian	0.0011%	91,058

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.Ala627Thr
Coding: c.1879G>A
MANE Select: NM_001292034
dbSNP: rs775340413
Type: single nucleotide variant
Location: chr6:149399124 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 53.24 · 6 PDB

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-ala627thr (accessed [today's date]).

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