Is TBCB p.Ser128Arg (c.382A>C) pathogenic?

TBCB p.Ser128Arg (c.382A>C) is classified Uncertain significance in TBCB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.4053); Absent from gnomAD v4.1.

How common is TBCB p.Ser128Arg (c.382A>C) in the general population?

TBCB p.Ser128Arg (c.382A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TBCB p.Ser128Arg (c.382A>C)?

AlphaMissense predicts ambiguous (score 0.4053) — an in-silico prediction, not a clinical call.

TBCB p.Ser128Arg

c.382A>C · VCV4181026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4053 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4053	ambiguous
REVEL	0.209	benign-leaning
SaProt	LLR -4.02	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.93 · regional, not allelic
Overall
CADD	22.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TBCB
Protein: p.Ser128Arg
Coding: c.382A>C
MANE Select: NM_001281
Type: single nucleotide variant
Location: chr19:36121553 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.55
Residue 128: a modified residue (phosphoserine; by pak1)

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

Similar variants

TBCB p.Tyr197Asn Uncertain significance ★★ ⚠ same type
TBCB p.Ala218Gly Uncertain significance ★ ⚠ same type
TBCB p.Arg103Gly Uncertain significance ★ ⚠ same type
TBCB p.Arg103Pro Uncertain significance ★ ⚠ same type
TBCB p.Arg138Gln Uncertain significance ★ ⚠ same type
TBCB p.Arg148His Uncertain significance ★ ⚠ same type
TBCB p.Arg196Cys Uncertain significance ★ ⚠ same type
TBCB p.Arg212Cys 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/tbcb-p-ser128arg (accessed [today's date]).

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