Is CD2AP p.Pro350Ser (c.1048C>T) pathogenic?

CD2AP p.Pro350Ser (c.1048C>T) is classified Uncertain significance in CD2AP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0734); Very rare (popmax 0.00317%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CD2AP p.Pro350Ser (c.1048C>T)?

CD2AP p.Pro350Ser (c.1048C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD2AP p.Pro350Ser (c.1048C>T) in the general population?

CD2AP p.Pro350Ser (c.1048C>T) is very rare (popmax 0.00317%, nfe) (gnomAD).

What do computational predictors say about CD2AP p.Pro350Ser (c.1048C>T)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

CD2AP p.Pro350Ser

c.1048C>T · VCV4222784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00317%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.68	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 2.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	15.76	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 0.00317% European (non-Finnish) · 37/1,168,328 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00204%

Overall 0.00262% 38/1,448,756 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00317%	31,576
Remaining individualsnot grpmax-eligible	0.00161%	62,048

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.Pro350Ser
Coding: c.1048C>T
MANE Select: NM_012120
Type: single nucleotide variant
Location: chr6:47582005 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 350: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD2AP p.Arg228Gln Uncertain significance ★★ ⚠ same condition
CD2AP p.Arg504Cys Uncertain significance ★★ same condition
CD2AP p.Arg84Gln Uncertain significance ★★ ⚠ same condition
CD2AP p.Asn427Ser Uncertain significance ★★ ⚠ same condition
CD2AP p.Asn506Ser Uncertain significance ★★ ⚠ same condition
CD2AP p.Asp473Gly Uncertain significance ★★ ⚠ same condition
CD2AP p.Gly605Arg Uncertain significance ★★ ⚠ same condition
CD2AP p.His174Pro 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-pro350ser (accessed [today's date]).

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