Is DAB1 p.Ile89Val (c.265A>G) pathogenic?

DAB1 p.Ile89Val (c.265A>G) is classified Uncertain significance in DAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0854); Very rare (popmax 0.00692%, amr).

How common is DAB1 p.Ile89Val (c.265A>G) in the general population?

DAB1 p.Ile89Val (c.265A>G) is very rare (popmax 0.00692%, amr) (gnomAD).

What do computational predictors say about DAB1 p.Ile89Val (c.265A>G)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

DAB1 p.Ile89Val

c.265A>G · VCV4658310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00692%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -4.82	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 3.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 119 kb · p 2.8e-08 · regional, not allelic
Overall
CADD	16.32	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00692% Admixed American · 4/57,762 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00139%

Overall 0.000388% 6/1,545,812 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00692%	14,440
African / African-American	0.00271%	36,900

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.Ile89Val
Coding: c.265A>G
MANE Select: NM_001365792
Type: single nucleotide variant
Location: chr1:57136584 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.20
Residue 89: the pid domain

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

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-ile89val (accessed [today's date]).

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