Is DAB2 p.Ser436Cys (c.1306A>T) pathogenic?

DAB2 p.Ser436Cys (c.1306A>T) is classified Uncertain significance in DAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.2309); Very rare (popmax 0.00446%, eas).

How common is DAB2 p.Ser436Cys (c.1306A>T) in the general population?

DAB2 p.Ser436Cys (c.1306A>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DAB2 p.Ser436Cys (c.1306A>T)?

AlphaMissense predicts likely benign (score 0.2309) — an in-silico prediction, not a clinical call.

DAB2 p.Ser436Cys

c.1306A>T · rs755764497 · VCV3079885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2309 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2309	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.51 · evaluated, not missing
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	26.9	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 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00131% 2/152,210 alleles · very rare

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.Ser436Cys
Coding: c.1306A>T
MANE Select: NM_001343
dbSNP: rs755764497
Type: single nucleotide variant
Location: chr5:39382653 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 54.33 · 3 PDB
Residue 436: 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-ser436cys (accessed [today's date]).

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