Is TAB1 p.Arg348Cys (c.1042C>T) pathogenic?

TAB1 p.Arg348Cys (c.1042C>T) is classified Uncertain significance in TAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: ambiguous (0.4518); Very rare (popmax 0.00223%, eas).

How common is TAB1 p.Arg348Cys (c.1042C>T) in the general population?

TAB1 p.Arg348Cys (c.1042C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about TAB1 p.Arg348Cys (c.1042C>T)?

AlphaMissense predicts ambiguous (score 0.4518) — an in-silico prediction, not a clinical call.

TAB1 p.Arg348Cys

c.1042C>T · VCV3803798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4518 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.4518	ambiguous
REVEL	0.31	indeterminate
SaProt	LLR -9.45	tolerated
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 0.89	unconstrained · MANE · 30 kb · p 0.0045 · regional, not allelic
Overall
CADD	32.0	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 0.00223% East Asian · 1/44,890 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000992% 16/1,613,694 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
South Asian	0.0022%	45,545
African / African-American	0.00133%	74,946
European (non-Finnish)	0.00102%	98,337

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.Arg348Cys
Coding: c.1042C>T
MANE Select: NM_006116
Type: single nucleotide variant
Location: chr22:39426823 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82 · 35 PDB
Residue 348: 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-arg348cys (accessed [today's date]).

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