Is CD2AP p.Glu73= (c.219A>G) pathogenic?

CD2AP p.Glu73= (c.219A>G) is classified Benign/Likely benign in CD2AP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-15). Low-frequency (popmax 2.83%, afr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

How common is CD2AP p.Glu73= (c.219A>G) in the general population?

CD2AP p.Glu73= (c.219A>G) is low-frequency (popmax 2.83%, afr) (gnomAD).

CD2AP p.Glu73=

Q: What condition is associated with CD2AP p.Glu73= (c.219A>G)?

CD2AP p.Glu73= (c.219A>G) is associated with focal segmental glomerulosclerosis 3, susceptibility to, focal segmental glomerulosclerosis (ClinVar).

c.219A>G · rs7749045 · VCV260189

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.83%, afr)

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

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 2.9	GERP -4.2, phastCons 1
Overall
CADD	8.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.83% African / African-American · 2,126/75,054 alleles

Filtering AF 2.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.69%

Overall 0.146% 2,358/1,614,094 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.83%	35
Admixed American	0.207%	484
Remaining individualsnot grpmax-eligible	0.146%	687
Middle Eastern	0.066%	1,515
South Asian	0.00549%	18,216
European (non-Finnish)	0.000678%	147,498

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.Glu73=
Coding: c.219A>G
MANE Select: NM_012120
dbSNP: rs7749045
Type: single nucleotide variant
Location: chr6:47533655 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 73: the 'interaction with anln and localization to the midbody' region

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

Also linked: focal segmental glomerulosclerosis

Similar variants

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
CD2AP c.*496A>G 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-glu73 (accessed [today's date]).

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