Is TBCD p.Pro967Arg (c.2900C>G) pathogenic?

TBCD p.Pro967Arg (c.2900C>G) is classified Uncertain significance in TBCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.1329); Absent from gnomAD v4.1; Associated with TBCD-related disorder.

What condition is associated with TBCD p.Pro967Arg (c.2900C>G)?

TBCD p.Pro967Arg (c.2900C>G) is associated with TBCD-related disorder (ClinVar).

How common is TBCD p.Pro967Arg (c.2900C>G) in the general population?

TBCD p.Pro967Arg (c.2900C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TBCD p.Pro967Arg (c.2900C>G)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

TBCD p.Pro967Arg

c.2900C>G · rs926584346 · VCV2630103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TBCD-related disorder

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -15.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	23.0	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

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: TBCD
Protein: p.Pro967Arg
Coding: c.2900C>G
MANE Select: NM_005993
dbSNP: rs926584346
Type: single nucleotide variant
Location: chr17:82929409 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.45 · 6 PDB

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

Disease context

TBCD-related disorder

Similar variants

TBCD p.Arg113Ter Pathogenic/Likely pathogenic ★★ same condition
TBCD p.His77Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
TBCD p.Ala1093Thr Uncertain significance ★★ ⚠ same condition
TBCD p.Leu292Val Conflicting classifications of pathogenicity ★ ⚠ same condition
ZNF750 p.Arg158Gln Benign same condition
ZNF750 p.Asn175= Benign same condition
ZNF750 p.Met235Val Benign same condition
ZNF750 p.Pro288Leu Benign 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/tbcd-p-pro967arg (accessed [today's date]).

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