Is TBCD p.Arg968Cys (c.2902C>T) pathogenic?

TBCD p.Arg968Cys (c.2902C>T) is classified Benign/Likely benign in TBCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0887); Low-frequency (popmax 1.64%, eas).

How common is TBCD p.Arg968Cys (c.2902C>T) in the general population?

TBCD p.Arg968Cys (c.2902C>T) is low-frequency (popmax 1.64%, eas) (gnomAD).

What do computational predictors say about TBCD p.Arg968Cys (c.2902C>T)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

TBCD p.Arg968Cys

c.2902C>T · rs181489692 · VCV713534

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.64%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -10.40	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 2.6	GERP 1.3, phastCons 0.98
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	18.33	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 1.64% East Asian · 734/44,876 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5%

Overall 0.0547% 882/1,613,042 alleles · low-frequency exomes 768/1,460,700 · genomes 114/152,342 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.64%	61
Remaining individualsnot grpmax-eligible	0.0576%	1,736
South Asian	0.034%	2,938
Middle Eastern	0.033%	3,030
Finnishnot grpmax-eligible	0.0127%	7,882
European (non-Finnish)	0.00585%	17,100
Admixed American	0.00167%	60,022
African / African-American	0.00133%	75,060

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.Arg968Cys
Coding: c.2902C>T
MANE Select: NM_005993
dbSNP: rs181489692
Type: single nucleotide variant
Location: chr17:82929411 (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

Similar variants

TBCD p.Arg968His Conflicting classifications of pathogenicity ★ ⚠ same residue
TBCD p.Arg968= Likely benign ★ same residue
TBCD c.1224-2A>G Pathogenic/Likely pathogenic ★★ same type
TBCD c.2007-2A>G Likely pathogenic ★★ same type
TBCD p.Ala475Thr Pathogenic/Likely pathogenic ★★ same type
TBCD p.Ala554Val Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg113Ter Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg303Ter Pathogenic/Likely pathogenic ★★ 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/tbcd-p-arg968cys (accessed [today's date]).

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