Is DAB2 p.Arg296Cys (c.886C>T) pathogenic?

DAB2 p.Arg296Cys (c.886C>T) is classified Benign in DAB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). AlphaMissense: likely benign (0.1019); Low-frequency (popmax 1.77%, afr).

How common is DAB2 p.Arg296Cys (c.886C>T) in the general population?

DAB2 p.Arg296Cys (c.886C>T) is low-frequency (popmax 1.77%, afr) (gnomAD).

What do computational predictors say about DAB2 p.Arg296Cys (c.886C>T)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

DAB2 p.Arg296Cys

c.886C>T · rs79344176 · VCV789138

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.77%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.58	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 5.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 15 kb · p 0.83 · regional, not allelic
Overall
CADD	24.7	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 1.77% African / African-American · 1,326/75,014 alleles

Filtering AF 1.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.66%

Overall 0.136% 2,188/1,614,080 alleles · low-frequency exomes 1,404/1,461,876 · genomes 784/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.77%	57
East Asian	1.46%	68
Remaining individualsnot grpmax-eligible	0.162%	619
Admixed American	0.0816%	1,225
Middle Eastern	0.0495%	2,021
South Asian	0.0373%	2,679
Finnishnot grpmax-eligible	0.00156%	64,016
European (non-Finnish)	0.00153%	65,556

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.Arg296Cys
Coding: c.886C>T
MANE Select: NM_001343
dbSNP: rs79344176
Type: single nucleotide variant
Location: chr5:39383073 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 54.33 · 3 PDB
Residue 296: 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.Arg296= Benign ★★ same residue
DAB2 p.Leu206Pro Uncertain significance ★★ ⚠ same type
DAB2 c.571-9T>A 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
DAB2 p.Thr505Ile 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-arg296cys (accessed [today's date]).

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