Is TUBA3E p.Pro72Ser (c.214C>T) pathogenic?

TUBA3E p.Pro72Ser (c.214C>T) is classified Uncertain significance in TUBA3E (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.3594); Very rare (popmax 0.00667%, amr).

How common is TUBA3E p.Pro72Ser (c.214C>T) in the general population?

TUBA3E p.Pro72Ser (c.214C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about TUBA3E p.Pro72Ser (c.214C>T)?

AlphaMissense predicts ambiguous (score 0.3594) — an in-silico prediction, not a clinical call.

TUBA3E p.Pro72Ser

c.214C>T · rs1367978408 · VCV2216761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3594 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3594	ambiguous
REVEL	0.755	pathogenic-leaning
SaProt	LLR -12.10	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.7	phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 4,074 bp · p 5.9e-06 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.00667% Admixed American · 4/59,982 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000372% 6/1,613,154 alleles · very rare exomes 2/1,460,974 · genomes 4/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,995
South Asian	0.0011%	91,038
European (non-Finnish)	8.48e-05%	1,179,334

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: TUBA3E
Protein: p.Pro72Ser
Coding: c.214C>T
MANE Select: NM_207312
dbSNP: rs1367978408
Type: single nucleotide variant
Location: chr2:130196161 (GRCh38)

Full TUBA3E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/tuba3e-p-pro72ser (accessed [today's date]).

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