Is CD2AP p.Arg212= (c.636A>T) pathogenic?

CD2AP p.Arg212= (c.636A>T) is classified Benign/Likely benign in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). Rare (popmax 0.504%, afr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Arg212= (c.636A>T)?

CD2AP p.Arg212= (c.636A>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Arg212= (c.636A>T) in the general population?

CD2AP p.Arg212= (c.636A>T) is rare (popmax 0.504%, afr) (gnomAD).

CD2AP p.Arg212=

c.636A>T · rs146010044 · VCV1170021

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.504%, 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 3	GERP 1, phastCons 1
Overall
CADD	10.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.504% African / African-American · 378/75,046 alleles

Filtering AF 0.462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.445%

Overall 0.0256% 413/1,614,030 alleles · rare exomes 186/1,461,686 · genomes 227/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.504%	199
Admixed American	0.0283%	3,531
Remaining individualsnot grpmax-eligible	0.0272%	3,676
Middle Eastern	0.0165%	6,060

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.Arg212=
Coding: c.636A>T
MANE Select: NM_012120
dbSNP: rs146010044
Type: single nucleotide variant
Location: chr6:47574158 (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.Arg212Gln Uncertain significance ★ ⚠ same residue
CD2AP p.Arg212Leu Uncertain significance ★ ⚠ 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

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-arg212 (accessed [today's date]).

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