Is TBCD p.Glu1007Ala (c.3020A>C) pathogenic?

TBCD p.Glu1007Ala (c.3020A>C) is classified Conflicting classifications of pathogenicity in TBCD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-15). AlphaMissense: likely benign (0.0918); Rare (popmax 0.33%, eas).

How common is TBCD p.Glu1007Ala (c.3020A>C) in the general population?

TBCD p.Glu1007Ala (c.3020A>C) is rare (popmax 0.33%, eas) (gnomAD).

What do computational predictors say about TBCD p.Glu1007Ala (c.3020A>C)?

AlphaMissense predicts likely benign (score 0.0918) — an in-silico prediction, not a clinical call.

TBCD p.Glu1007Ala

c.3020A>C · rs141474186 · VCV1560494

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0918 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.33%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0918	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.94	GERP -2.2, phastCons 0.3
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	8.967	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 0.33% East Asian · 148/44,852 alleles

Filtering AF 0.287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.0107% 172/1,613,630 alleles · rare exomes 160/1,461,482 · genomes 12/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.33%	303
Remaining individualsnot grpmax-eligible	0.024%	4,165
European (non-Finnish)	0.000763%	131,092

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.Glu1007Ala
Coding: c.3020A>C
MANE Select: NM_005993
dbSNP: rs141474186
Type: single nucleotide variant
Location: chr17:82930550 (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

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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-glu1007ala (accessed [today's date]).

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