Is CD2AP p.Ser443= (c.1329A>G) pathogenic?

CD2AP p.Ser443= (c.1329A>G) is classified Likely benign in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-28). Ultra-rare (popmax 0.0923%, sas).

How common is CD2AP p.Ser443= (c.1329A>G) in the general population?

CD2AP p.Ser443= (c.1329A>G) is ultra-rare (popmax 0.0923%, sas) (gnomAD).

CD2AP p.Ser443=

c.1329A>G · rs545654808 · VCV2706844

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0923%, sas)

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 2.6	GERP -1.9, phastCons 1
Overall
CADD	10.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0923% South Asian · 84/91,028 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0705%

Overall 0.0062% 100/1,612,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0923%	1,084
Middle Eastern	0.0165%	6,044
Remaining individualsnot grpmax-eligible	0.00321%	31,200
Admixed American	0.00167%	59,820
European (non-Finnish)	0.00102%	98,215

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.Ser443=
Coding: c.1329A>G
MANE Select: NM_012120
dbSNP: rs545654808
Type: single nucleotide variant
Location: chr6:47599355 (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

Similar variants

CD2AP c.1274+3A>G Uncertain significance ★★ same type
CD2AP c.1633-6T>A Uncertain significance ★★ same type
CD2AP c.-130C>G Uncertain significance ★★ same type
CD2AP c.-166A>G Uncertain significance ★★ same type
CD2AP c.*319A>C Uncertain significance ★★ same type
CD2AP c.*452C>G Uncertain significance ★★ same type
CD2AP c.*494G>A Uncertain significance ★★ same type
CD2AP c.*496A>G Uncertain significance ★★ same type

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-ser443 (accessed [today's date]).

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