Is TAB2 p.His6Arg (c.17A>G) pathogenic?

TAB2 p.His6Arg (c.17A>G) is classified Uncertain significance in TAB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.1226); Very rare (popmax 0.00356%, nfe); Associated with congenital heart defects, multiple types, 2.

What condition is associated with TAB2 p.His6Arg (c.17A>G)?

TAB2 p.His6Arg (c.17A>G) is associated with congenital heart defects, multiple types, 2 (ClinVar).

How common is TAB2 p.His6Arg (c.17A>G) in the general population?

TAB2 p.His6Arg (c.17A>G) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about TAB2 p.His6Arg (c.17A>G)?

AlphaMissense predicts likely benign (score 0.1226) — an in-silico prediction, not a clinical call.

TAB2 p.His6Arg

c.17A>G · rs763061741 · VCV2436924

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital heart defects, multiple types, 2

Computational evidence

Protein change
AlphaMissense	0.1226	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	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	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00356% European (non-Finnish) · 42/1,179,984 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.0026% 42/1,613,996 alleles · very rare exomes 41/1,461,774 · genomes 1/152,222 · 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.His6Arg
Coding: c.17A>G
MANE Select: NM_001292034
dbSNP: rs763061741
Type: single nucleotide variant
Location: chr6:149370014 (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

Disease context

congenital heart defects, multiple types, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TAB2 p.His6= Likely benign ★ same residue
TAB2 c.1764+1G>A Pathogenic/Likely pathogenic ★★ same condition
TAB2 p.Arg574Ter Likely pathogenic ★★ same condition
TAB2 p.Arg96Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.Ile68Thr Uncertain significance ★★ same condition
TAB2 p.Ser50Asn Uncertain significance ★★ ⚠ same condition
TAB2 p.Gln7= Benign/Likely benign ★★ same condition
TAB2 p.Gln127Ter Pathogenic ★ same condition

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-his6arg (accessed [today's date]).

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