Is DAB2IP p.Pro1021Ser (c.3061C>T) pathogenic?

DAB2IP p.Pro1021Ser (c.3061C>T) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.0856); Very rare (popmax 0.00134%, afr).

How common is DAB2IP p.Pro1021Ser (c.3061C>T) in the general population?

DAB2IP p.Pro1021Ser (c.3061C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DAB2IP p.Pro1021Ser (c.3061C>T)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

DAB2IP p.Pro1021Ser

c.3061C>T · rs1488426664 · VCV2615676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.01	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 3.9	GERP 0.84, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,835 bp · p 0.021 · regional, not allelic
Overall
CADD	23.0	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 0.00134% African / African-American · 1/74,874 alleles

Overall 6.85e-05% 1/1,460,864 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: DAB2IP
Protein: p.Pro1021Ser
Coding: c.3061C>T
MANE Select: NM_001395010
dbSNP: rs1488426664
Type: single nucleotide variant
Location: chr9:121774353 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 1021: the 'disordered' region

Full DAB2IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAB2IP p.Ala816Thr Benign ★★ same type
DAB2IP p.Arg199= Benign ★★ same type
DAB2IP p.Arg966His Benign ★★ same type
DAB2IP p.Asp97= Benign/Likely benign ★★ same type
DAB2IP p.Lys284= Benign ★★ same type
DAB2IP p.Pro126= Likely benign ★★ same type
DAB2IP p.Ser460Leu Benign ★★ ⚠ same type
DAB2IP p.Ser68= Likely 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/dab2ip-p-pro1021ser (accessed [today's date]).

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