Is CD2AP p.Glu367Lys (c.1099G>A) pathogenic?

CD2AP p.Glu367Lys (c.1099G>A) is classified Uncertain significance in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-12). AlphaMissense: likely benign (0.173); Very rare (popmax 0.00672%, afr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Glu367Lys (c.1099G>A)?

CD2AP p.Glu367Lys (c.1099G>A) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Glu367Lys (c.1099G>A) in the general population?

CD2AP p.Glu367Lys (c.1099G>A) is very rare (popmax 0.00672%, afr) (gnomAD).

What do computational predictors say about CD2AP p.Glu367Lys (c.1099G>A)?

AlphaMissense predicts likely benign (score 0.173) — an in-silico prediction, not a clinical call.

CD2AP p.Glu367Lys

c.1099G>A · rs144903299 · VCV2888584

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.173 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00672%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.173	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00672% African / African-American · 5/74,434 alleles

Filtering AF 0.00401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00367%

Overall 0.00415% 66/1,589,558 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00672%	14,887
European (non-Finnish)	0.0051%	19,626
Remaining individualsnot grpmax-eligible	0.00325%	30,808

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.Glu367Lys
Coding: c.1099G>A
MANE Select: NM_012120
dbSNP: rs144903299
Type: single nucleotide variant
Location: chr6:47582056 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 367: 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-glu367lys (accessed [today's date]).

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