Is DAB2IP p.Leu96Pro (c.287T>C) pathogenic?

DAB2IP p.Leu96Pro (c.287T>C) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.9498); Very rare (popmax 9.09e-05%, nfe).

How common is DAB2IP p.Leu96Pro (c.287T>C) in the general population?

DAB2IP p.Leu96Pro (c.287T>C) is very rare (popmax 9.09e-05%, nfe) (gnomAD).

What do computational predictors say about DAB2IP p.Leu96Pro (c.287T>C)?

AlphaMissense predicts likely pathogenic (score 0.9498) — an in-silico prediction, not a clinical call.

DAB2IP p.Leu96Pro

c.287T>C · VCV4237373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.09e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9498	likely pathogenic
REVEL	0.316	indeterminate
SaProt	LLR -10.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 105 kb · p 0.0028 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 9.09e-05% European (non-Finnish) · 1/1,099,604 alleles

Overall 7.57e-05% 1/1,320,616 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.Leu96Pro
Coding: c.287T>C
MANE Select: NM_001395010
Type: single nucleotide variant
Location: chr9:121699383 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74

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

Similar variants

DAB2IP p.Leu96Met 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-leu96pro (accessed [today's date]).

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