Is TUBB p.Cys239Ser (c.716G>C) pathogenic?

TUBB p.Cys239Ser (c.716G>C) is classified Pathogenic in TUBB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-18). AlphaMissense: ambiguous (0.4572); Absent from gnomAD v4.1.

How common is TUBB p.Cys239Ser (c.716G>C) in the general population?

TUBB p.Cys239Ser (c.716G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TUBB p.Cys239Ser (c.716G>C)?

AlphaMissense predicts ambiguous (score 0.4572) — an in-silico prediction, not a clinical call.

TUBB p.Cys239Ser

c.716G>C · VCV3343929

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4572 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4572	ambiguous
REVEL	0.555	indeterminate
SaProt	LLR -8.65	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	phastCons 1
Overall
CADD	24.2	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

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: TUBB
Protein: p.Cys239Ser
Coding: c.716G>C
MANE Select: NM_001069 · reported on NM_178014
Type: single nucleotide variant
Location: chr6:30723778 (GRCh38)
Structure: AlphaFold pLDDT 92.44 · 3 PDB

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

Similar variants

TUBB2A p.Cys239= Likely benign ★ same residue
TUBB p.Asn52Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
TUBB p.Asp327Asn Pathogenic/Likely pathogenic ★★ same type
TUBB p.Gln15His Likely pathogenic ★★ same type
TUBB p.Glu111Lys Pathogenic/Likely pathogenic ★★ same type
TUBB p.Glu401Lys Pathogenic ★★ same type
TUBB p.Met299Val Pathogenic ★★ same type
TUBB p.Thr221Ile Pathogenic/Likely 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/tubb-p-cys239ser (accessed [today's date]).

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