Is DAB2 p.Pro335Ser (c.1003C>T) pathogenic?

DAB2 p.Pro335Ser (c.1003C>T) is classified Uncertain significance in DAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0735); Rare (popmax 0.128%, nfe).

How common is DAB2 p.Pro335Ser (c.1003C>T) in the general population?

DAB2 p.Pro335Ser (c.1003C>T) is rare (popmax 0.128%, nfe) (gnomAD).

What do computational predictors say about DAB2 p.Pro335Ser (c.1003C>T)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

DAB2 p.Pro335Ser

c.1003C>T · rs145888939 · VCV3079883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.128%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -4.35	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 7.4	GERP 0.73, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 15 kb · p 0.83 · regional, not allelic
Overall
CADD	18.57	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 0.128% European (non-Finnish) · 1,505/1,180,010 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.0988% 1,595/1,614,098 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.128%	784
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Admixed American	0.0416%	2,401
African / African-American	0.0187%	5,359
Finnishnot grpmax-eligible	0.00781%	12,800
South Asian	0.00439%	22,769

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.Pro335Ser
Coding: c.1003C>T
MANE Select: NM_001343
dbSNP: rs145888939
Type: single nucleotide variant
Location: chr5:39382956 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 54.33 · 3 PDB
Residue 335: 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-pro335ser (accessed [today's date]).

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