Is TAB2 p.Arg576Cys (c.1726C>T) pathogenic?

TAB2 p.Arg576Cys (c.1726C>T) is classified Uncertain significance in TAB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-25). AlphaMissense: likely pathogenic (0.9605); Very rare (popmax 8.47e-05%, nfe).

How common is TAB2 p.Arg576Cys (c.1726C>T) in the general population?

TAB2 p.Arg576Cys (c.1726C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about TAB2 p.Arg576Cys (c.1726C>T)?

AlphaMissense predicts likely pathogenic (score 0.9605) — an in-silico prediction, not a clinical call.

TAB2 p.Arg576Cys

c.1726C>T · rs772797083 · VCV1695814

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9605 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9605	likely pathogenic
REVEL	0.577	indeterminate
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.83, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	33.0	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 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 0.000186% 3/1,613,828 alleles · very rare exomes 3/1,461,584 · genomes 0/152,244 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00313%	31,956
European (non-Finnish)grpmax	8.47e-05%	1,179,999

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg576Cys
Coding: c.1726C>T
MANE Select: NM_001292034
dbSNP: rs772797083
Type: single nucleotide variant
Location: chr6:149397726 (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 p.Arg576His Uncertain significance ★ ⚠ same residue
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

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-arg576cys (accessed [today's date]).

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