Is TBCD p.Val809Ile (c.2425G>A) pathogenic?

TBCD p.Val809Ile (c.2425G>A) is classified Likely benign in TBCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-21). AlphaMissense: likely benign (0.076); Rare (popmax 0.138%, sas).

How common is TBCD p.Val809Ile (c.2425G>A) in the general population?

TBCD p.Val809Ile (c.2425G>A) is rare (popmax 0.138%, sas) (gnomAD).

What do computational predictors say about TBCD p.Val809Ile (c.2425G>A)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

TBCD p.Val809Ile

c.2425G>A · rs534429525 · VCV1426995

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -7.15	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 -0.058	GERP -3
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	7.605	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 0.138% South Asian · 126/91,090 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.0128% 206/1,614,046 alleles · rare exomes 178/1,461,676 · genomes 28/152,370 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.138%	723
East Asian	0.0334%	2,992
African / African-American	0.024%	4,171
Remaining individualsnot grpmax-eligible	0.016%	6,248
Admixed American	0.00333%	30,011
European (non-Finnish)	0.00297%	33,711

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.Val809Ile
Coding: c.2425G>A
MANE Select: NM_005993
dbSNP: rs534429525
Type: single nucleotide variant
Location: chr17:82926445 (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 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
TBCD p.Arg323Ter Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg436Ter 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-val809ile (accessed [today's date]).

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