Is CD2AP p.Pro244Ser (c.730C>T) pathogenic?

CD2AP p.Pro244Ser (c.730C>T) is classified Uncertain significance in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-15). AlphaMissense: likely benign (0.0778); Ultra-rare (popmax 0.0233%, amr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Pro244Ser (c.730C>T)?

CD2AP p.Pro244Ser (c.730C>T) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Pro244Ser (c.730C>T) in the general population?

CD2AP p.Pro244Ser (c.730C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about CD2AP p.Pro244Ser (c.730C>T)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

CD2AP p.Pro244Ser

c.730C>T · rs757507978 · VCV847282

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -7.34	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 0.59	GERP 2, phastCons 0.52
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	19.19	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 0.0233% Admixed American · 14/59,990 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00131% 21/1,600,598 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,285
African / African-American	0.00535%	18,682
South Asian	0.0033%	30,271

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.Pro244Ser
Coding: c.730C>T
MANE Select: NM_012120
dbSNP: rs757507978
Type: single nucleotide variant
Location: chr6:47576524 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 244: 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-pro244ser (accessed [today's date]).

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