Is TAB1 p.Ala260Val (c.779C>T) pathogenic?

TAB1 p.Ala260Val (c.779C>T) is classified Uncertain significance in TAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely benign (0.0779); Very rare (popmax 0.00769%, sas).

How common is TAB1 p.Ala260Val (c.779C>T) in the general population?

TAB1 p.Ala260Val (c.779C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about TAB1 p.Ala260Val (c.779C>T)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

TAB1 p.Ala260Val

c.779C>T · rs759816864 · VCV2517586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.81	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 5.9	GERP 1.7, phastCons 0.79
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.0045 · regional, not allelic
Overall
CADD	21.8	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 0.00769% South Asian · 7/91,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000496% 8/1,614,026 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: TAB1
Protein: p.Ala260Val
Coding: c.779C>T
MANE Select: NM_006116
dbSNP: rs759816864
Type: single nucleotide variant
Location: chr22:39421829 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82 · 35 PDB
Residue 260: the ppm-type phosphatase domain; a turn

Full TAB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TAB1 c.325-5C>T Benign ★★ same type
TAB1 p.His355= Benign ★★ same type
TAB1 p.Ala171Val Uncertain significance ★ ⚠ same type
TAB1 p.Ala225Ser Uncertain significance ★ ⚠ same type
TAB1 p.Ala325Thr Uncertain significance ★ ⚠ same type
TAB1 p.Ala397Thr Uncertain significance ★ ⚠ same type
TAB1 p.Ala503Thr Uncertain significance ★ ⚠ same type
TAB1 p.Ala98Val 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/tab1-p-ala260val (accessed [today's date]).

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