Is CD2AP p.Ile268Phe (c.802A>T) pathogenic?

CD2AP p.Ile268Phe (c.802A>T) is classified Conflicting classifications of pathogenicity in CD2AP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0712); Rare (popmax 0.123%, amr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Ile268Phe (c.802A>T)?

CD2AP p.Ile268Phe (c.802A>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Ile268Phe (c.802A>T) in the general population?

CD2AP p.Ile268Phe (c.802A>T) is rare (popmax 0.123%, amr) (gnomAD).

What do computational predictors say about CD2AP p.Ile268Phe (c.802A>T)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

CD2AP p.Ile268Phe

c.802A>T · rs759309620 · VCV1116135

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Pangolin	Δ0.21	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.4	GERP 0.74, phastCons 0.76
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	15.83	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 0.123% Admixed American · 74/59,988 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0924%

Overall 0.00474% 76/1,604,456 alleles · rare exomes 74/1,452,246 · genomes 2/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.123%	811
Remaining individualsnot grpmax-eligible	0.00161%	62,118
European (non-Finnish)	8.53e-05%	1,171,822

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.Ile268Phe
Coding: c.802A>T
MANE Select: NM_012120
dbSNP: rs759309620
Type: single nucleotide variant
Location: chr6:47576596 (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-ile268phe (accessed [today's date]).

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