Is TUBA8 p.Pro89= (c.267A>G) pathogenic?

TUBA8 p.Pro89= (c.267A>G) is classified Uncertain significance in TUBA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-19). Very rare (popmax 0.000424%, nfe).

How common is TUBA8 p.Pro89= (c.267A>G) in the general population?

TUBA8 p.Pro89= (c.267A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

TUBA8 p.Pro89=

c.267A>G · rs372938703 · VCV2752006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -0.45
Overall
CADD	12.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,038 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00118% 19/1,614,106 alleles · very rare exomes 17/1,461,890 · genomes 2/152,216 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0203%	4,926
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)grpmax	0.000424%	236,008

Finnish 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: TUBA8
Protein: p.Pro89=
Coding: c.267A>G
MANE Select: NM_018943
dbSNP: rs372938703
Type: single nucleotide variant
Location: chr22:18124196 (GRCh38)
Gene constraint: LOEUF 1.117 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.24

Full TUBA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TUBA8 p.Ala273Thr Uncertain significance ★★ ⚠ same type
TUBA8 p.Ala383Val Uncertain significance ★★ ⚠ same type
TUBA8 p.Ala385Glu Uncertain significance ★★ ⚠ same type
TUBA8 p.Ala385Val Uncertain significance ★★ same type
TUBA8 p.Ala400Thr Uncertain significance ★★ ⚠ same type
TUBA8 p.Arg121Cys Uncertain significance ★★ ⚠ same type
TUBA8 p.Arg121His Uncertain significance ★★ ⚠ same type
TUBA8 p.Arg156Cys Uncertain significance ★★ 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/tuba8-p-pro89 (accessed [today's date]).

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