Is CD2AP p.His604= (c.1812C>T) pathogenic?

CD2AP p.His604= (c.1812C>T) is classified Likely benign in CD2AP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.0814%, afr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.His604= (c.1812C>T)?

CD2AP p.His604= (c.1812C>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.His604= (c.1812C>T) in the general population?

CD2AP p.His604= (c.1812C>T) is ultra-rare (popmax 0.0814%, afr) (gnomAD).

CD2AP p.His604=

c.1812C>T · rs140391156 · VCV1514673

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0814%, 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 0.14	GERP 0.42, phastCons 0.99
Overall
CADD	11.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0814% African / African-American · 61/74,940 alleles

Filtering AF 0.065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0591%

Overall 0.0059% 95/1,610,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0814%	1,229
Remaining individualsnot grpmax-eligible	0.00962%	10,393
South Asian	0.0022%	45,501
European (non-Finnish)	0.00212%	47,092
Admixed American	0.00167%	59,992

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.His604=
Coding: c.1812C>T
MANE Select: NM_012120
dbSNP: rs140391156
Type: single nucleotide variant
Location: chr6:47609302 (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 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-his604 (accessed [today's date]).

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