Is TBCE p.Val460= (c.1380C>T) pathogenic?

TBCE p.Val460= (c.1380C>T) is classified Likely benign in TBCE (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-14). Ultra-rare (popmax 0.0481%, afr).

How common is TBCE p.Val460= (c.1380C>T) in the general population?

TBCE p.Val460= (c.1380C>T) is ultra-rare (popmax 0.0481%, afr) (gnomAD).

TBCE p.Val460=

c.1380C>T · rs373874343 · VCV1088574

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2	GERP -0.23, phastCons 0.4
Overall
CADD	8.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0481% African / African-American · 36/74,874 alleles

Filtering AF 0.0357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00242% 39/1,613,916 alleles · ultra-rare exomes 11/1,461,820 · genomes 28/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0481%	2,080
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	8.47e-05%	1,180,002

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: TBCE
Protein: p.Val460=
Coding: c.1380C>T
MANE Select: NM_003193
dbSNP: rs373874343
Type: single nucleotide variant
Location: chr1:235442892 (GRCh38)

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

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/tbce-p-val460 (accessed [today's date]).

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