Is TBCD p.Arg765Gln (c.2294G>A) pathogenic?

TBCD p.Arg765Gln (c.2294G>A) is classified Likely benign in TBCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.0635); Ultra-rare (popmax 0.0331%, mid); Associated with Inborn genetic diseases.

What condition is associated with TBCD p.Arg765Gln (c.2294G>A)?

TBCD p.Arg765Gln (c.2294G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TBCD p.Arg765Gln (c.2294G>A) in the general population?

TBCD p.Arg765Gln (c.2294G>A) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about TBCD p.Arg765Gln (c.2294G>A)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

TBCD p.Arg765Gln

c.2294G>A · VCV4632738

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -5.43	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 -0.69	GERP -2.3
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	2.018	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 0.0331% Middle Eastern · 2/6,038 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00108% 17/1,573,418 alleles · ultra-rare exomes 16/1,421,256 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,019
Remaining individualsnot grpmax-eligible	0.00492%	20,311
South Asian	0.00234%	42,811
East Asian	0.00233%	42,842
European (non-Finnish)	0.000777%	128,698

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: TBCD
Protein: p.Arg765Gln
Coding: c.2294G>A
MANE Select: NM_005993
Type: single nucleotide variant
Location: chr17:82924972 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TBCD p.Arg765Trp Uncertain significance ★★ ⚠ same residue
TBCD p.Gln330Ter Pathogenic ★★ same condition
TBCD p.Ala1159Val Uncertain significance ★★ ⚠ same condition
TBCD p.Ala1162Val Uncertain significance ★★ ⚠ same condition
TBCD p.Ala394Ser Uncertain significance ★★ ⚠ same condition
TBCD p.Ala415Val Uncertain significance ★★ ⚠ same condition
TBCD p.Ala599Thr Uncertain significance ★★ ⚠ same condition
TBCD p.Ala907Val Uncertain significance ★★ ⚠ 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-arg765gln (accessed [today's date]).

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