Is TBC1D32 p.Arg287Cys (c.859C>T) pathogenic?

TBC1D32 p.Arg287Cys (c.859C>T) is classified Uncertain significance in TBC1D32 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-27). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with TBC1D32 p.Arg287Cys (c.859C>T)?

TBC1D32 p.Arg287Cys (c.859C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TBC1D32 p.Arg287Cys (c.859C>T) in the general population?

TBC1D32 p.Arg287Cys (c.859C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TBC1D32 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

TBC1D32 p.Arg287Cys

c.859C>T · rs889563650 · VCV1511118

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.49	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 1.7	GERP -0.84, phastCons 0.89
Regional constraint	o/e 1.02	unconstrained · MANE · 228 kb · p 0.5 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,044 alleles

Filtering AF 0.00349% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00392% 63/1,607,222 alleles · ultra-rare exomes 53/1,455,864 · genomes 10/151,358 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,044
African / African-American	0.00807%	12,390
Admixed American	0.00505%	19,794
Remaining individualsnot grpmax-eligible	0.00482%	20,736
South Asian	0.00445%	22,483
European (non-Finnish)	0.00383%	26,142
East Asian	0.00223%	44,762

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: TBC1D32
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_152730
dbSNP: rs889563650
Type: single nucleotide variant
Location: chr6:121304536 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.84

Full TBC1D32 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TBC1D32 p.Arg287His Uncertain significance ★★ ⚠ same residue
TBC1D32 p.Arg820Cys Uncertain significance ★★ ⚠ same condition
TBC1D32 p.Arg884Trp Uncertain significance ★★ ⚠ same condition
TBC1D32 p.Asp661Val Uncertain significance ★★ ⚠ same condition
TBC1D32 p.Asp810Val Uncertain significance ★★ ⚠ same condition
TBC1D32 p.Asp862Glu Uncertain significance ★★ ⚠ same condition
TBC1D32 p.Cys986Arg Uncertain significance ★★ ⚠ same condition
TBC1D32 p.Glu138Lys Uncertain significance ★★ ⚠ 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/tbc1d32-p-arg287cys (accessed [today's date]).

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