Is TBCD p.Arg790Trp (c.2368C>T) pathogenic?

TBCD p.Arg790Trp (c.2368C>T) is classified Conflicting classifications of pathogenicity in TBCD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-02). AlphaMissense: likely benign (0.1165); Ultra-rare (popmax 0.0421%, afr); Associated with Inborn genetic diseases.

What condition is associated with TBCD p.Arg790Trp (c.2368C>T)?

TBCD p.Arg790Trp (c.2368C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TBCD p.Arg790Trp (c.2368C>T) in the general population?

TBCD p.Arg790Trp (c.2368C>T) is ultra-rare (popmax 0.0421%, afr) (gnomAD).

What do computational predictors say about TBCD p.Arg790Trp (c.2368C>T)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

TBCD p.Arg790Trp

c.2368C>T · rs200557085 · VCV1394140

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0421%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.323	indeterminate
SaProt	LLR -12.73	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -2.6
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	19.07	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 0.0421% African / African-American · 31/73,578 alleles

Filtering AF 0.0305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0265%

Overall 0.00694% 108/1,556,350 alleles · ultra-rare exomes 90/1,403,994 · genomes 18/152,356 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0421%	2,373
Middle Eastern	0.0171%	5,858
Admixed American	0.0135%	7,415
Remaining individualsnot grpmax-eligible	0.00663%	15,073
European (non-Finnish)	0.00548%	18,253
Finnishnot grpmax-eligible	0.00169%	59,104
South Asian	0.00118%	84,500

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.Arg790Trp
Coding: c.2368C>T
MANE Select: NM_005993
dbSNP: rs200557085
Type: single nucleotide variant
Location: chr17:82925046 (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.Arg790Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg790trp (accessed [today's date]).

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