Is TAB2 p.Arg549Ser (c.1647A>C) pathogenic?

TAB2 p.Arg549Ser (c.1647A>C) is classified Uncertain significance in TAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-04). AlphaMissense: ambiguous (0.5108); Absent from gnomAD v4.1.

How common is TAB2 p.Arg549Ser (c.1647A>C) in the general population?

TAB2 p.Arg549Ser (c.1647A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TAB2 p.Arg549Ser (c.1647A>C)?

AlphaMissense predicts ambiguous (score 0.5108) — an in-silico prediction, not a clinical call.

TAB2 p.Arg549Ser

c.1647A>C · rs2483485952 · VCV1708691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5108 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5108	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.45, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TAB2
Protein: p.Arg549Ser
Coding: c.1647A>C
MANE Select: NM_001292034
dbSNP: rs2483485952
Type: single nucleotide variant
Location: chr6:149397647 (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-arg549ser (accessed [today's date]).

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