Is CD2AP p.Ser469= (c.1407C>T) pathogenic?

CD2AP p.Ser469= (c.1407C>T) is classified Likely benign in CD2AP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-16). Very rare (popmax 0.00671%, afr); Associated with CD2AP-related disorder.

What condition is associated with CD2AP p.Ser469= (c.1407C>T)?

CD2AP p.Ser469= (c.1407C>T) is associated with CD2AP-related disorder (ClinVar).

How common is CD2AP p.Ser469= (c.1407C>T) in the general population?

CD2AP p.Ser469= (c.1407C>T) is very rare (popmax 0.00671%, afr) (gnomAD).

CD2AP p.Ser469=

c.1407C>T · rs1202214767 · VCV3031207

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00671%, afr)

Conditions

CD2AP-related disorder

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 0.3	GERP -4, phastCons 0.91
Overall
CADD	3.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00671% African / African-American · 5/74,504 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00031% 5/1,611,226 alleles · very rare exomes 0/1,460,024 · genomes 5/151,202 · joint denominator

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.Ser469=
Coding: c.1407C>T
MANE Select: NM_012120
dbSNP: rs1202214767
Type: single nucleotide variant
Location: chr6:47599433 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 469: a modified residue (phosphoserine)

Full CD2AP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD2AP-related disorder

Similar variants

CD2AP p.Leu184Ser Uncertain significance ★★ ⚠ same condition
CD2AP p.Lys239Glu Uncertain significance ★★ ⚠ same condition
CD2AP p.Asp3Glu Uncertain significance ★ ⚠ same condition
CD2AP p.Ser147Gly Uncertain significance ★ ⚠ same condition
CD2AP p.Ala398fs Likely pathogenic ★ same condition
CD2AP p.Lys105Leu Uncertain significance ★ same condition
CD2AP c.1274+3A>G Uncertain significance ★★ same type
CD2AP c.1633-6T>A 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-ser469 (accessed [today's date]).

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