Is DAB2 p.Val463Ile (c.1387G>A) pathogenic?

DAB2 p.Val463Ile (c.1387G>A) is classified Uncertain significance in DAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0773); Ultra-rare (popmax 0.0362%, sas).

How common is DAB2 p.Val463Ile (c.1387G>A) in the general population?

DAB2 p.Val463Ile (c.1387G>A) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

What do computational predictors say about DAB2 p.Val463Ile (c.1387G>A)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

DAB2 p.Val463Ile

c.1387G>A · VCV4237334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.9	GERP -3.6
Regional constraint	o/e 1.01	unconstrained · MANE · 15 kb · p 0.83 · regional, not allelic
Overall
CADD	7.493	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 0.0362% South Asian · 33/91,072 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00663% 107/1,613,792 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Middle Eastern	0.0164%	6,084
Finnishnot grpmax-eligible	0.0141%	7,110
Remaining individualsnot grpmax-eligible	0.0112%	8,925
East Asian	0.00668%	14,959
European (non-Finnish)	0.00415%	24,081
African / African-American	0.00401%	24,948
Admixed American	0.00333%	29,989

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.Val463Ile
Coding: c.1387G>A
MANE Select: NM_001343
Type: single nucleotide variant
Location: chr5:39381571 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 54.33 · 3 PDB
Residue 463: 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-val463ile (accessed [today's date]).

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