Is DIP2B p.Ala897Pro (c.2689G>C) pathogenic?

DIP2B p.Ala897Pro (c.2689G>C) is classified Uncertain significance in DIP2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-23). AlphaMissense: likely pathogenic (0.9968); Very rare (popmax 8.47e-05%, nfe); Associated with DIP2B-related disorder.

What condition is associated with DIP2B p.Ala897Pro (c.2689G>C)?

DIP2B p.Ala897Pro (c.2689G>C) is associated with DIP2B-related disorder (ClinVar).

How common is DIP2B p.Ala897Pro (c.2689G>C) in the general population?

DIP2B p.Ala897Pro (c.2689G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DIP2B p.Ala897Pro (c.2689G>C)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

DIP2B p.Ala897Pro

c.2689G>C · rs2540145523 · VCV3032427

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DIP2B-related disorder

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic · top 5% in DIP2B
REVEL	0.553	indeterminate
SaProt	LLR -15.49	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	29.2	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 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,884 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: DIP2B
Protein: p.Ala897Pro
Coding: c.2689G>C
MANE Select: NM_173602
dbSNP: rs2540145523
Type: single nucleotide variant
Location: chr12:50714434 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.83

Full DIP2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIP2B-related disorder

Similar variants

DIP2B p.Ala1101Asp Uncertain significance ★ same condition
DIP2B p.Ala1208Ser Uncertain significance ★ ⚠ same condition
DIP2B p.Glu172Ala Uncertain significance ★ ⚠ same condition
DIP2B p.Thr1016Asn Uncertain significance ★ ⚠ same condition
DIP2B p.Asp1565Gly Uncertain significance ⚠ same condition
DIP2B p.Ile792Val Conflicting classifications of pathogenicity ⚠ same condition
DIP2B p.Thr746Arg Uncertain significance ⚠ same condition
DIP2B c.1654+10C>T Likely benign same condition

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/dip2b-p-ala897pro (accessed [today's date]).

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