Is DAB1 p.Pro255Ser (c.763C>T) pathogenic?

DAB1 p.Pro255Ser (c.763C>T) is classified Likely pathogenic in DAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-12). AlphaMissense: likely pathogenic (0.9042); Very rare (popmax 0.00136%, afr); Associated with spastic ataxia.

What condition is associated with DAB1 p.Pro255Ser (c.763C>T)?

DAB1 p.Pro255Ser (c.763C>T) is associated with spastic ataxia (ClinVar).

How common is DAB1 p.Pro255Ser (c.763C>T) in the general population?

DAB1 p.Pro255Ser (c.763C>T) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about DAB1 p.Pro255Ser (c.763C>T)?

AlphaMissense predicts likely pathogenic (score 0.9042) — an in-silico prediction, not a clinical call.

DAB1 p.Pro255Ser

c.763C>T · rs1646774558 · VCV1027503

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

spastic ataxia

Computational evidence

Protein change
AlphaMissense	0.9042	likely pathogenic ✓ concordant with ClinVar
REVEL	0.36	indeterminate
SaProt	LLR -5.68	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.24 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P288S vs ClinVar P255S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,284 alleles

Overall 0.000252% 4/1,589,008 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00325%	30,767
African / African-Americangrpmax	0.00136%	73,284
European (non-Finnish)	8.55e-05%	1,169,836

Remaining individuals 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: DAB1
Protein: p.Pro255Ser
Coding: c.763C>T
MANE Select: NM_001365792
dbSNP: rs1646774558
Type: single nucleotide variant
Location: chr1:57026004 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.20

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

Disease context

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

Similar variants

DAB1 p.Ala103Val Uncertain significance ★★ ⚠ same type
DAB1 p.Ala75Thr Uncertain significance ★★ same type
DAB1 p.Arg41Gln Uncertain significance ★★ same type
DAB1 p.Pro334Leu Uncertain significance ★★ ⚠ same type
DAB1 p.Pro376Ala Uncertain significance ★★ ⚠ same type
DAB1 p.Pro391Ser Uncertain significance ★★ ⚠ same type
DAB1 p.Pro516Leu Uncertain significance ★★ ⚠ same type
DAB1 p.Val240Leu 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-pro255ser (accessed [today's date]).

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