Is CC2D1A p.Pro483Arg (c.1448C>G) pathogenic?

CC2D1A p.Pro483Arg (c.1448C>G) is classified Likely benign in CC2D1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-19). AlphaMissense: likely benign (0.1166); Very rare (popmax 0.00306%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Pro483Arg (c.1448C>G)?

CC2D1A p.Pro483Arg (c.1448C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D1A p.Pro483Arg (c.1448C>G) in the general population?

CC2D1A p.Pro483Arg (c.1448C>G) is very rare (popmax 0.00306%, nfe) (gnomAD).

What do computational predictors say about CC2D1A p.Pro483Arg (c.1448C>G)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

CC2D1A p.Pro483Arg

c.1448C>G · rs201884654 · VCV2300577

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00306%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -10.74	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.2, phastCons 0.94
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	20.3	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 0.00306% European (non-Finnish) · 36/1,178,364 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00199%

Overall 0.00224% 36/1,610,552 alleles · very rare exomes 34/1,458,406 · genomes 2/152,146 · 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: CC2D1A
Protein: p.Pro483Arg
Coding: c.1448C>G
MANE Select: NM_017721
dbSNP: rs201884654
Type: single nucleotide variant
Location: chr19:13920648 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 483: the 'disordered' region

Full CC2D1A 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

CC2D1A p.Pro483= Benign/Likely benign ★★ same residue
CC2D1A p.Pro483His Conflicting classifications of pathogenicity ★ ⚠ same residue
CC2D1A p.Pro483Leu Uncertain significance ★ ⚠ same residue
CC2D1A c.61-2A>G Likely pathogenic ★★ same condition
CC2D1A c.1941-6C>T Uncertain significance ★★ same condition
CC2D1A c.2073+5G>T Uncertain significance ★★ same condition
CC2D1A c.946+6A>G Uncertain significance ★★ same condition
CC2D1A p.Ala154Thr 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/cc2d1a-p-pro483arg (accessed [today's date]).

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