Is CD2AP p.Arg84Ter (c.250C>T) pathogenic?

CD2AP p.Arg84Ter (c.250C>T) is classified Likely pathogenic in CD2AP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-17). Very rare (popmax 0.00439%, sas); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Arg84Ter (c.250C>T)?

CD2AP p.Arg84Ter (c.250C>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Arg84Ter (c.250C>T) in the general population?

CD2AP p.Arg84Ter (c.250C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

CD2AP p.Arg84Ter

c.250C>T · rs368795308 · VCV1179189

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.1, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,090 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000805% 13/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,773
African / African-American	0.00133%	74,922
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.Arg84Ter
Coding: c.250C>T
MANE Select: NM_012120
dbSNP: rs368795308
Type: single nucleotide variant
Location: chr6:47533686 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 84: 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

Similar variants

CD2AP p.Arg84Gln 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
CD2AP c.*494G>A 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-arg84ter (accessed [today's date]).

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