Is TAB2 p.Ala618Val (c.1853C>T) pathogenic?

TAB2 p.Ala618Val (c.1853C>T) is classified Uncertain significance in TAB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). AlphaMissense: ambiguous (0.4018); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with TAB2 p.Ala618Val (c.1853C>T)?

TAB2 p.Ala618Val (c.1853C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TAB2 p.Ala618Val (c.1853C>T) in the general population?

TAB2 p.Ala618Val (c.1853C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about TAB2 p.Ala618Val (c.1853C>T)?

AlphaMissense predicts ambiguous (score 0.4018) — an in-silico prediction, not a clinical call.

TAB2 p.Ala618Val

c.1853C>T · VCV4179278

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4018	ambiguous
REVEL	0.238	benign-leaning
SaProt	LLR -5.60	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 12 kb · p 7.4e-11 · regional, not allelic
Overall
CADD	24.9	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 0.00333% Admixed American · 2/59,990 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,072 alleles · very rare exomes 0/1,460,948 · genomes 2/152,124 · 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.Ala618Val
Coding: c.1853C>T
MANE Select: NM_001292034
Type: single nucleotide variant
Location: chr6:149398057 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TAB2 p.Arg72His Uncertain significance ★★ ⚠ same condition
TAB2 p.Arg96Ser Uncertain significance ★★ same condition
TAB2 p.Asn118Tyr Uncertain significance ★★ ⚠ same condition
TAB2 p.Asn669Thr Uncertain significance ★★ ⚠ same condition
TAB2 p.Gln209Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.Glu49Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.Glu93Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.Gly56Ser Uncertain significance ★★ ⚠ 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-ala618val (accessed [today's date]).

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