Is CD2AP p.Pro99= (c.297A>G) pathogenic?

CD2AP p.Pro99= (c.297A>G) is classified Benign/Likely benign in CD2AP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-30). Rare (popmax 0.215%, sas); Associated with focal segmental glomerulosclerosis.

What condition is associated with CD2AP p.Pro99= (c.297A>G)?

CD2AP p.Pro99= (c.297A>G) is associated with focal segmental glomerulosclerosis (ClinVar).

How common is CD2AP p.Pro99= (c.297A>G) in the general population?

CD2AP p.Pro99= (c.297A>G) is rare (popmax 0.215%, sas) (gnomAD).

CD2AP p.Pro99=

c.297A>G · rs539471431 · VCV1712388

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.215%, sas)

Conditions

focal segmental glomerulosclerosis

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 2.3	GERP -0.32, phastCons 1
Overall
CADD	11.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.215% South Asian · 196/91,078 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.181%

Overall 0.0127% 205/1,614,132 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.215%	465
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	8.47e-05%	1,179,993

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.Pro99=
Coding: c.297A>G
MANE Select: NM_012120
dbSNP: rs539471431
Type: single nucleotide variant
Location: chr6:47533733 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 99: 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD2AP p.Glu73= Benign/Likely benign ★★ same condition
CD2AP p.Lys633Arg Benign/Likely benign ★★ same condition
CD2AP p.Ser232= Benign/Likely benign ★★ same condition
CD2AP p.Thr374Ala Benign/Likely benign ★★ same condition
CD2AP p.Ala491Thr Uncertain significance ★ ⚠ same condition
CD2AP p.Glu143Asp Uncertain significance ★ ⚠ same condition
CD2AP p.Glu143Gly Uncertain significance ★ ⚠ same condition
CD2AP p.Glu525del 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-pro99 (accessed [today's date]).

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