Is TBC1D32 p.Ser80Phe (c.239C>T) pathogenic?

TBC1D32 p.Ser80Phe (c.239C>T) is classified Uncertain significance in TBC1D32 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1395); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TBC1D32 p.Ser80Phe (c.239C>T)?

TBC1D32 p.Ser80Phe (c.239C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TBC1D32 p.Ser80Phe (c.239C>T) in the general population?

TBC1D32 p.Ser80Phe (c.239C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TBC1D32 p.Ser80Phe (c.239C>T)?

AlphaMissense predicts likely benign (score 0.1395) — an in-silico prediction, not a clinical call.

TBC1D32 p.Ser80Phe

c.239C>T · VCV4180896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1395 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1395	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 228 kb · p 0.5 · regional, not allelic
Overall
CADD	22.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TBC1D32
Protein: p.Ser80Phe
Coding: c.239C>T
MANE Select: NM_152730
Type: single nucleotide variant
Location: chr6:121321711 (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.Arg287Cys Uncertain significance ★★ ⚠ same condition
TBC1D32 p.Arg287His Uncertain significance ★★ ⚠ same condition
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

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-ser80phe (accessed [today's date]).

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