Is TAB1 p.Phe342Cys (c.1025T>G) pathogenic?

TAB1 p.Phe342Cys (c.1025T>G) is classified Uncertain significance in TAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: ambiguous (0.4474); Very rare (popmax 0.01%, amr).

How common is TAB1 p.Phe342Cys (c.1025T>G) in the general population?

TAB1 p.Phe342Cys (c.1025T>G) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about TAB1 p.Phe342Cys (c.1025T>G)?

AlphaMissense predicts ambiguous (score 0.4474) — an in-silico prediction, not a clinical call.

TAB1 p.Phe342Cys

c.1025T>G · VCV3324143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4474 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4474	ambiguous
REVEL	0.186	benign-leaning
SaProt	LLR -7.87	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 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.0045 · regional, not allelic
Overall
CADD	24.6	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 0.01% Admixed American · 6/60,014 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000991% 16/1,613,896 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	74,940
European (non-Finnish)	0.000593%	168,579

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.Phe342Cys
Coding: c.1025T>G
MANE Select: NM_006116
Type: single nucleotide variant
Location: chr22:39426806 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82 · 35 PDB
Residue 342: the ppm-type phosphatase domain; an α-helix

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.Ala260Val 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

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-phe342cys (accessed [today's date]).

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