Is CD2AP p.Pro532= (c.1596A>G) pathogenic?

CD2AP p.Pro532= (c.1596A>G) is classified Likely benign in CD2AP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). Very rare (popmax 0.00667%, amr).

How common is CD2AP p.Pro532= (c.1596A>G) in the general population?

CD2AP p.Pro532= (c.1596A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

CD2AP p.Pro532=

c.1596A>G · rs775834580 · VCV1972140

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 -1.1	GERP -3.7
Overall
CADD	2.921	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,966 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,612,880 alleles · very rare exomes 3/1,460,762 · genomes 1/152,118 · joint denominator

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: CD2AP
Protein: p.Pro532=
Coding: c.1596A>G
MANE Select: NM_012120
dbSNP: rs775834580
Type: single nucleotide variant
Location: chr6:47607992 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB

Full CD2AP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD2AP p.Pro532Ser Uncertain significance ★★ ⚠ same residue
CD2AP c.1274+3A>G Uncertain significance ★★ same type
CD2AP c.1633-6T>A Uncertain significance ★★ same type
CD2AP c.-130C>G Uncertain significance ★★ same type
CD2AP c.-166A>G Uncertain significance ★★ same type
CD2AP c.*319A>C Uncertain significance ★★ same type
CD2AP c.*452C>G Uncertain significance ★★ same type
CD2AP c.*494G>A 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/cd2ap-p-pro532 (accessed [today's date]).

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