Is CD2BP2 p.Ile87Val (c.259A>G) pathogenic?

CD2BP2 p.Ile87Val (c.259A>G) is classified Uncertain significance in CD2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely pathogenic (0.586); Absent from gnomAD v4.1.

How common is CD2BP2 p.Ile87Val (c.259A>G) in the general population?

CD2BP2 p.Ile87Val (c.259A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD2BP2 p.Ile87Val (c.259A>G)?

AlphaMissense predicts likely pathogenic (score 0.586) — an in-silico prediction, not a clinical call.

CD2BP2 p.Ile87Val

c.259A>G · rs2543873293 · VCV2486075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.586 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.586	likely pathogenic
REVEL	0.131	moderately benign-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,693 bp · p 0.012 · regional, not allelic
Overall
CADD	23.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD2BP2
Protein: p.Ile87Val
Coding: c.259A>G
MANE Select: NM_006110
dbSNP: rs2543873293
Type: single nucleotide variant
Location: chr16:30354017 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.04 · 10 PDB
Residue 87: a β-strand

Full CD2BP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD2BP2 p.Ala256Val Uncertain significance ★ ⚠ same type
CD2BP2 p.Ala67Val Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg129Gln Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg177Gly Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg181Gln Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg187Lys Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg201Leu Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg201Trp Uncertain significance ★ ⚠ 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/cd2bp2-p-ile87val (accessed [today's date]).

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