Is TBCD p.Arg580Ter (c.1738C>T) pathogenic?

TBCD p.Arg580Ter (c.1738C>T) is classified Pathogenic in TBCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-21). Very rare (popmax 0.00134%, afr).

How common is TBCD p.Arg580Ter (c.1738C>T) in the general population?

TBCD p.Arg580Ter (c.1738C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

TBCD p.Arg580Ter

c.1738C>T · rs770137069 · VCV1975424

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 19 of 39
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.7, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,782 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000437% 7/1,601,862 alleles · very rare exomes 6/1,449,652 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,782
South Asian	0.00113%	88,592
European (non-Finnish)	0.000426%	234,867

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.Arg580Ter
Coding: c.1738C>T
MANE Select: NM_005993
dbSNP: rs770137069
Type: single nucleotide variant
Location: chr17:82903412 (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.Arg580Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TBCD p.Arg580= 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-arg580ter (accessed [today's date]).

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