Is TUBB8 p.Pro243= (c.729G>A) pathogenic?

TUBB8 p.Pro243= (c.729G>A) is classified Benign in TUBB8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-10). Common (popmax 74.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with oocyte maturation defect 2.

What condition is associated with TUBB8 p.Pro243= (c.729G>A)?

TUBB8 p.Pro243= (c.729G>A) is associated with oocyte maturation defect 2 (ClinVar).

TUBB8 p.Pro243=

Q: How common is TUBB8 p.Pro243= (c.729G>A) in the general population?

TUBB8 p.Pro243= (c.729G>A) is common (popmax 74.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.729G>A · rs6560827 · VCV1185186

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 74.7%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

oocyte maturation defect 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	2.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 74.7% Middle Eastern · 3,190/4,268 alleles

Filtering AF 72.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 72.8%

Overall 70.3% 1,056,836/1,504,054 alleles · common exomes 953,192/1,359,770 · genomes 103,644/144,284 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	82.8%	1
Middle Easterngrpmax	74.7%	1
European (non-Finnish)	73%	1
Ashkenazi Jewishnot grpmax-eligible	72.2%	1
Finnishnot grpmax-eligible	70.2%	1
Remaining individualsnot grpmax-eligible	70.2%	1
African / African-American	62.8%	2
South Asian	62%	2
Admixed American	56.6%	2
East Asian	44.1%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TUBB8
Protein: p.Pro243=
Coding: c.729G>A
MANE Select: NM_177987
dbSNP: rs6560827
Type: single nucleotide variant
Location: chr10:47663 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.99

Full TUBB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oocyte maturation defect 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TUBB8 p.Pro243Leu Uncertain significance ★ ⚠ same residue
TUBB8 p.Val255Met Likely pathogenic ★★ same condition
TUBB8 p.Ala313Val Uncertain significance ★★ ⚠ same condition
TUBB8 p.Arg380His Uncertain significance ★★ same condition
TUBB8 c.277+10G>A Benign ★★ same condition
TUBB8 c.277+129G>A Benign ★★ same condition
TUBB8 c.278-82G>A Benign ★★ same condition
TUBB8 c.57+26T>C Benign ★★ 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/tubb8-p-pro243 (accessed [today's date]).

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