TBCD p.Asp953=

Q: Is TBCD p.Asp953= (c.2859T>C) pathogenic?

TBCD p.Asp953= (c.2859T>C) is classified Benign in TBCD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 28.6%, amr) — too common for a highly-penetrant pathogenic allele; Associated with early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome.

Q: What condition is associated with TBCD p.Asp953= (c.2859T>C)?

TBCD p.Asp953= (c.2859T>C) is associated with early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome (ClinVar).

Q: How common is TBCD p.Asp953= (c.2859T>C) in the general population?

TBCD p.Asp953= (c.2859T>C) is common (popmax 28.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2859T>C · rs1127986 · VCV1167402

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 28.6%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -2.7
Overall
CADD	0.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.6% Admixed American · 17,123/59,974 alleles

Filtering AF 28.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 28%

Overall 25% 402,846/1,612,410 alleles · common exomes 365,007/1,460,220 · genomes 37,839/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	28.6%	4
Finnishnot grpmax-eligible	27.3%	4
Middle Eastern	26.6%	4
Ashkenazi Jewishnot grpmax-eligible	26.5%	4
Remaining individualsnot grpmax-eligible	25.4%	4
South Asian	25.2%	4
European (non-Finnish)	25%	4
African / African-American	23.8%	4
East Asian	16.5%	6
Amishnot grpmax-eligible	8.99%	11

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.Asp953=
Coding: c.2859T>C
MANE Select: NM_005993
dbSNP: rs1127986
Type: single nucleotide variant
Location: chr17:82929368 (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

early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TBCD p.Asp953Asn Uncertain significance ★★ ⚠ same residue
TBCD c.1224-2A>G Pathogenic/Likely pathogenic ★★ same condition
TBCD c.2007-2A>G Likely pathogenic ★★ same condition
TBCD p.Ala475Thr Pathogenic/Likely pathogenic ★★ same condition
TBCD p.Ala554Val Pathogenic/Likely pathogenic ★★ same condition
TBCD p.Arg303Ter Pathogenic/Likely pathogenic ★★ same condition
TBCD p.Arg323Ter Pathogenic/Likely pathogenic ★★ same condition
TBCD p.Arg436Ter Pathogenic ★★ 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-asp953 (accessed [today's date]).

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