Is DAB2 p.Ile430Val (c.1288A>G) pathogenic?

DAB2 p.Ile430Val (c.1288A>G) is classified Likely benign in DAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-18). AlphaMissense: likely benign (0.2221); Rare (popmax 0.137%, nfe).

How common is DAB2 p.Ile430Val (c.1288A>G) in the general population?

DAB2 p.Ile430Val (c.1288A>G) is rare (popmax 0.137%, nfe) (gnomAD).

What do computational predictors say about DAB2 p.Ile430Val (c.1288A>G)?

AlphaMissense predicts likely benign (score 0.2221) — an in-silico prediction, not a clinical call.

DAB2 p.Ile430Val

c.1288A>G · rs148242258 · VCV718436

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2221 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.137%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2221	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -5.28	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 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 15 kb · p 0.83 · regional, not allelic
Overall
CADD	24.3	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 0.137% European (non-Finnish) · 1,613/1,180,008 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.129% 2,087/1,614,034 alleles · rare exomes 1,872/1,461,842 · genomes 215/152,192 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.467%	214
Ashkenazi Jewishnot grpmax-eligible	0.23%	435
European (non-Finnish)grpmax	0.137%	732
Remaining individualsnot grpmax-eligible	0.106%	947
Admixed American	0.04%	2,500
African / African-American	0.0227%	4,407

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: DAB2
Protein: p.Ile430Val
Coding: c.1288A>G
MANE Select: NM_001343
dbSNP: rs148242258
Type: single nucleotide variant
Location: chr5:39382671 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 54.33 · 3 PDB
Residue 430: the 'required for localization to clathrin-coated pits' region; the 'disordered' region

Full DAB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAB2 p.Leu206Pro Uncertain significance ★★ ⚠ same type
DAB2 c.571-9T>A Benign ★★ same type
DAB2 p.Arg296= Benign ★★ same type
DAB2 p.Arg296Cys Benign ★★ same type
DAB2 p.Asn226= Benign ★★ same type
DAB2 p.Gln523His Likely benign ★★ same type
DAB2 p.Pro529= Likely benign ★★ same type
DAB2 p.Ser227= 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/dab2-p-ile430val (accessed [today's date]).

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