Is DIP2B p.Ala689= (c.2067C>A) pathogenic?

DIP2B p.Ala689= (c.2067C>A) is classified Likely benign in DIP2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-04). Ultra-rare (popmax 0.0147%, afr); Associated with DIP2B-related disorder.

What condition is associated with DIP2B p.Ala689= (c.2067C>A)?

DIP2B p.Ala689= (c.2067C>A) is associated with DIP2B-related disorder (ClinVar).

How common is DIP2B p.Ala689= (c.2067C>A) in the general population?

DIP2B p.Ala689= (c.2067C>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

DIP2B p.Ala689=

c.2067C>A · rs764498936 · VCV3044174

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

DIP2B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3.7, phastCons 0.38
Overall
CADD	7.538	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,854 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000682% 11/1,612,694 alleles · ultra-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.Ala689=
Coding: c.2067C>A
MANE Select: NM_173602
dbSNP: rs764498936
Type: single nucleotide variant
Location: chr12:50698346 (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.Ala897Pro 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

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-ala689 (accessed [today's date]).

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