Is DAB2IP p.Pro925Arg (c.2774C>G) pathogenic?

DAB2IP p.Pro925Arg (c.2774C>G) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2537); Very rare (popmax 0.00201%, amr).

How common is DAB2IP p.Pro925Arg (c.2774C>G) in the general population?

DAB2IP p.Pro925Arg (c.2774C>G) is very rare (popmax 0.00201%, amr) (gnomAD).

What do computational predictors say about DAB2IP p.Pro925Arg (c.2774C>G)?

AlphaMissense predicts likely benign (score 0.2537) — an in-silico prediction, not a clinical call.

DAB2IP p.Pro925Arg

c.2774C>G · VCV4237357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2537 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00201%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2537	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,835 bp · p 0.021 · regional, not allelic
Overall
CADD	21.9	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 0.00201% Admixed American · 1/49,716 alleles

Overall 7.32e-05% 1/1,365,966 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.Pro925Arg
Coding: c.2774C>G
MANE Select: NM_001395010
Type: single nucleotide variant
Location: chr9:121773302 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 925: the 'disordered' region; the 'necessary for interaction with akt1' region

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

Similar variants

DAB2IP p.Pro925Leu Uncertain significance ★ ⚠ same residue
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

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-pro925arg (accessed [today's date]).

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