Is CD2AP p.Leu402= (c.1204C>T) pathogenic?

CD2AP p.Leu402= (c.1204C>T) is classified Benign in CD2AP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Leu402= (c.1204C>T)?

CD2AP p.Leu402= (c.1204C>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

CD2AP p.Leu402=

Q: How common is CD2AP p.Leu402= (c.1204C>T) in the general population?

CD2AP p.Leu402= (c.1204C>T) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1204C>T · rs2039503 · VCV260181

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.38	GERP -3.6, phastCons 0.28
Overall
CADD	3.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,814/44,814 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.7% 1,607,337/1,612,860 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Finnishnot grpmax-eligible	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
European (non-Finnish)	100%	1
South Asian	100%	1
Middle Eastern	99.6%	1
Remaining individualsnot grpmax-eligible	99.6%	1
Admixed American	99.6%	1
African / African-American	93.4%	1

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.Leu402=
Coding: c.1204C>T
MANE Select: NM_012120
dbSNP: rs2039503
Type: single nucleotide variant
Location: chr6:47595956 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 402: 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

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-leu402 (accessed [today's date]).

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