Is DAB2IP p.Pro840Leu (c.2519C>T) pathogenic?

DAB2IP p.Pro840Leu (c.2519C>T) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1477); Ultra-rare (popmax 0.0417%, amr).

How common is DAB2IP p.Pro840Leu (c.2519C>T) in the general population?

DAB2IP p.Pro840Leu (c.2519C>T) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about DAB2IP p.Pro840Leu (c.2519C>T)?

AlphaMissense predicts likely benign (score 0.1477) — an in-silico prediction, not a clinical call.

DAB2IP p.Pro840Leu

c.2519C>T · rs766855032 · VCV2386782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1477 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1477	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -7.65	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 4.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,835 bp · p 0.021 · regional, not allelic
Overall
CADD	27.3	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 0.0417% Admixed American · 25/59,998 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00552% 89/1,612,356 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,395
African / African-American	0.012%	8,325
South Asian	0.00769%	13,012
Remaining individualsnot grpmax-eligible	0.00641%	15,613
European (non-Finnish)	0.00331%	30,253
Finnishnot grpmax-eligible	0.0016%	62,588

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.Pro840Leu
Coding: c.2519C>T
MANE Select: NM_001395010
dbSNP: rs766855032
Type: single nucleotide variant
Location: chr9:121773047 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 840: 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.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-pro840leu (accessed [today's date]).

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