Is CD2AP p.Ser232= (c.696C>T) pathogenic?

CD2AP p.Ser232= (c.696C>T) is classified Benign/Likely benign in CD2AP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-01). Low-frequency (popmax 3.23%, mid); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

How common is CD2AP p.Ser232= (c.696C>T) in the general population?

CD2AP p.Ser232= (c.696C>T) is low-frequency (popmax 3.23%, mid) (gnomAD).

CD2AP p.Ser232=

Q: What condition is associated with CD2AP p.Ser232= (c.696C>T)?

CD2AP p.Ser232= (c.696C>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to, focal segmental glomerulosclerosis (ClinVar).

c.696C>T · rs140627775 · VCV260191

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.23%, mid)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.51	GERP -2.4, phastCons 0.007
Overall
CADD	7.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.23% Middle Eastern · 196/6,060 alleles

Filtering AF 2.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.72%

Overall 1.04% 16,788/1,613,852 alleles · low-frequency exomes 15,425/1,461,630 · genomes 1,363/152,222 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.23%	31
Ashkenazi Jewishnot grpmax-eligible	1.62%	62
Remaining individualsnot grpmax-eligible	1.18%	84
Admixed American	1.16%	86
European (non-Finnish)	1.12%	89
South Asian	0.898%	111
African / African-American	0.569%	176
Finnishnot grpmax-eligible	0.25%	400
East Asian	0.00446%	22,419

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.Ser232=
Coding: c.696C>T
MANE Select: NM_012120
dbSNP: rs140627775
Type: single nucleotide variant
Location: chr6:47574218 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 232: the 'disordered' 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-ser232 (accessed [today's date]).

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