Is CD2AP p.Pro532Ser (c.1594C>T) pathogenic?

CD2AP p.Pro532Ser (c.1594C>T) is classified Uncertain significance in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0814); Ultra-rare (popmax 0.0165%, mid); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Pro532Ser (c.1594C>T)?

CD2AP p.Pro532Ser (c.1594C>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Pro532Ser (c.1594C>T) in the general population?

CD2AP p.Pro532Ser (c.1594C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD2AP p.Pro532Ser (c.1594C>T)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

CD2AP p.Pro532Ser

c.1594C>T · rs1332219962 · VCV911606

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -0.56, phastCons 0.54
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	11.33	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,056 alleles

Overall 6.2e-05% 1/1,612,850 alleles · ultra-rare exomes 1/1,460,690 · genomes 0/152,160 · 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.Pro532Ser
Coding: c.1594C>T
MANE Select: NM_012120
dbSNP: rs1332219962
Type: single nucleotide variant
Location: chr6:47607990 (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

Disease context

focal segmental glomerulosclerosis 3, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD2AP p.Pro532= Likely benign ★ same residue
CD2AP c.1274+3A>G Uncertain significance ★★ same condition
CD2AP c.1633-6T>A Uncertain significance ★★ same condition
CD2AP c.-130C>G Uncertain significance ★★ same condition
CD2AP c.-166A>G Uncertain significance ★★ same condition
CD2AP c.*319A>C Uncertain significance ★★ same condition
CD2AP c.*452C>G Uncertain significance ★★ same condition
CD2AP c.*494G>A 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/cd2ap-p-pro532ser (accessed [today's date]).

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