Is CD2AP p.Val466Ile (c.1396G>A) pathogenic?

CD2AP p.Val466Ile (c.1396G>A) is classified Conflicting classifications of pathogenicity in CD2AP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-02). AlphaMissense: likely benign (0.0624); Ultra-rare (popmax 0.0294%, afr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Val466Ile (c.1396G>A)?

CD2AP p.Val466Ile (c.1396G>A) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Val466Ile (c.1396G>A) in the general population?

CD2AP p.Val466Ile (c.1396G>A) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

What do computational predictors say about CD2AP p.Val466Ile (c.1396G>A)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

CD2AP p.Val466Ile

c.1396G>A · rs150046838 · VCV2285103

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.33	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 -0.79	GERP -3.6
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	0.522	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0294% African / African-American · 22/74,766 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.00211% 34/1,612,064 alleles · ultra-rare exomes 19/1,460,218 · genomes 15/151,846 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0294%	3,398
Admixed American	0.0117%	8,538
Remaining individualsnot grpmax-eligible	0.00321%	31,182
South Asian	0.0011%	91,026
European (non-Finnish)	0.00017%	589,511

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.Val466Ile
Coding: c.1396G>A
MANE Select: NM_012120
dbSNP: rs150046838
Type: single nucleotide variant
Location: chr6:47599422 (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.Val466Leu 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-val466ile (accessed [today's date]).

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