Is TBCE p.Ile503= (c.1509C>T) pathogenic?

TBCE p.Ile503= (c.1509C>T) is classified Likely benign in TBCE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Very rare (popmax 0.00267%, afr).

How common is TBCE p.Ile503= (c.1509C>T) in the general population?

TBCE p.Ile503= (c.1509C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

TBCE p.Ile503=

c.1509C>T · rs769918946 · VCV2976713

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, 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 -0.032	GERP -0.84, phastCons 0.22
Overall
CADD	6.574	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,884 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,613,782 alleles · very rare exomes 5/1,461,686 · genomes 3/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,442
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,472
South Asian	0.0011%	91,054
European (non-Finnish)	0.000254%	393,298

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.Ile503=
Coding: c.1509C>T
MANE Select: NM_003193
dbSNP: rs769918946
Type: single nucleotide variant
Location: chr1:235448687 (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-ile503 (accessed [today's date]).

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