Is DAB1 p.Ala15Thr (c.43G>A) pathogenic?

DAB1 p.Ala15Thr (c.43G>A) is classified Conflicting classifications of pathogenicity in DAB1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-09). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.0882%, afr); Associated with spinocerebellar ataxia type 37.

What condition is associated with DAB1 p.Ala15Thr (c.43G>A)?

DAB1 p.Ala15Thr (c.43G>A) is associated with spinocerebellar ataxia type 37 (ClinVar).

How common is DAB1 p.Ala15Thr (c.43G>A) in the general population?

DAB1 p.Ala15Thr (c.43G>A) is ultra-rare (popmax 0.0882%, afr) (gnomAD).

How is Spinocerebellar ataxia type 37 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DAB1 p.Ala15Thr (c.43G>A)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

DAB1 p.Ala15Thr

c.43G>A · rs376587394 · VCV2440675

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0882%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spinocerebellar ataxia type 37

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.99	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 -1.3	GERP -3.2
Regional constraint	o/e 1.09	unconstrained · MANE · 146 kb · p 0.59 · regional, not allelic
Overall
CADD	15.65	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 0.0882% African / African-American · 66/74,824 alleles

Filtering AF 0.0711% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0649%

Overall 0.00863% 139/1,611,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0882%	1,134
Remaining individualsnot grpmax-eligible	0.00801%	12,479
South Asian	0.00773%	12,942
Admixed American	0.00672%	14,872
European (non-Finnish)	0.00475%	21,045
East Asian	0.00224%	44,690

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: DAB1
Protein: p.Ala15Thr
Coding: c.43G>A
MANE Select: NM_001365792
dbSNP: rs376587394
Type: single nucleotide variant
Location: chr1:57290988 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.20
Residue 15: the 'disordered' region

Full DAB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia type 37 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 37 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

DAB1 p.Arg41Gln Uncertain significance ★★ same condition
DAB1 p.Val240Leu Uncertain significance ★★ ⚠ same condition
DAB1 p.His107Tyr Uncertain significance ★ same condition
DAB1 c.-136-4G>T Benign ★ same condition
DAB1 p.Gly70Asp Uncertain significance ⚠ same condition
DAB1 p.Ala103Val Uncertain significance ★★ ⚠ same type
DAB1 p.Ala75Thr Uncertain significance ★★ same type
DAB1 p.Pro334Leu 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/dab1-p-ala15thr (accessed [today's date]).

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