Is DAB2IP p.Ala478Val (c.1433C>T) pathogenic?

DAB2IP p.Ala478Val (c.1433C>T) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: ambiguous (0.406); Ultra-rare (popmax 0.0144%, nfe).

How common is DAB2IP p.Ala478Val (c.1433C>T) in the general population?

DAB2IP p.Ala478Val (c.1433C>T) is ultra-rare (popmax 0.0144%, nfe) (gnomAD).

What do computational predictors say about DAB2IP p.Ala478Val (c.1433C>T)?

AlphaMissense predicts ambiguous (score 0.406) — an in-silico prediction, not a clinical call.

DAB2IP p.Ala478Val

c.1433C>T · rs368910721 · VCV2369172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.406 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, nfe)

Computational evidence

Protein change
AlphaMissense	0.406	ambiguous
REVEL	0.622	indeterminate
SaProt	LLR -9.68	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 2.6e-17 · regional, not allelic
Overall
CADD	27.1	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 0.0144% European (non-Finnish) · 170/1,180,034 alleles

Filtering AF 0.0126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.0113% 183/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0144%	6,941
Remaining individualsnot grpmax-eligible	0.0096%	10,415
African / African-American	0.00801%	12,490
Admixed American	0.00167%	60,002

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: DAB2IP
Protein: p.Ala478Val
Coding: c.1433C>T
MANE Select: NM_001395010
dbSNP: rs368910721
Type: single nucleotide variant
Location: chr9:121763852 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 478: the ras-gap domain

Full DAB2IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAB2IP p.Ala816Thr Benign ★★ same type
DAB2IP p.Arg199= Benign ★★ same type
DAB2IP p.Arg966His Benign ★★ same type
DAB2IP p.Asp97= Benign/Likely benign ★★ same type
DAB2IP p.Lys284= Benign ★★ same type
DAB2IP p.Pro126= Likely benign ★★ same type
DAB2IP p.Ser460Leu Benign ★★ ⚠ same type
DAB2IP p.Ser68= Likely benign ★★ 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/dab2ip-p-ala478val (accessed [today's date]).

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