Is CD2AP p.Arg504Cys (c.1510C>T) pathogenic?

CD2AP p.Arg504Cys (c.1510C>T) is classified Uncertain significance in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). AlphaMissense: ambiguous (0.3425); Ultra-rare (popmax 0.0385%, sas); Associated with Inborn genetic diseases.

What condition is associated with CD2AP p.Arg504Cys (c.1510C>T)?

CD2AP p.Arg504Cys (c.1510C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD2AP p.Arg504Cys (c.1510C>T) in the general population?

CD2AP p.Arg504Cys (c.1510C>T) is ultra-rare (popmax 0.0385%, sas) (gnomAD).

What do computational predictors say about CD2AP p.Arg504Cys (c.1510C>T)?

AlphaMissense predicts ambiguous (score 0.3425) — an in-silico prediction, not a clinical call.

CD2AP p.Arg504Cys

c.1510C>T · VCV4607871

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3425 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0385%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3425	ambiguous
REVEL	0.303	indeterminate
SaProt	LLR -9.73	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	32.0	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 0.0385% South Asian · 35/90,840 alleles

Filtering AF 0.0284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.00281% 45/1,601,108 alleles · ultra-rare exomes 41/1,449,188 · genomes 4/151,920 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0385%	2,595
Admixed American	0.00334%	29,936
Remaining individualsnot grpmax-eligible	0.00161%	62,038
African / African-American	0.00134%	74,576
European (non-Finnish)	0.000513%	194,765

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.Arg504Cys
Coding: c.1510C>T
MANE Select: NM_012120
Type: single nucleotide variant
Location: chr6:47606257 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 504: an α-helix

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.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
CD2AP p.Ile134Asn 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-arg504cys (accessed [today's date]).

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