Is CC2D2A p.Pro301Arg (c.902C>G) pathogenic?

CC2D2A p.Pro301Arg (c.902C>G) is classified Uncertain significance in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.2883); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CC2D2A p.Pro301Arg (c.902C>G)?

CC2D2A p.Pro301Arg (c.902C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D2A p.Pro301Arg (c.902C>G) in the general population?

CC2D2A p.Pro301Arg (c.902C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D2A p.Pro301Arg (c.902C>G)?

AlphaMissense predicts likely benign (score 0.2883) — an in-silico prediction, not a clinical call.

CC2D2A p.Pro301Arg

c.902C>G · VCV4606653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2883 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2883	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	26.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CC2D2A
Protein: p.Pro301Arg
Coding: c.902C>G
MANE Select: NM_001378615
Type: single nucleotide variant
Location: chr4:15515889 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46

Full CC2D2A 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

CC2D2A p.Pro301Ser Uncertain significance ★ ⚠ same residue
CC2D2A p.Val1045Ala Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Ala323Thr Uncertain significance ★★ ⚠ same condition
CC2D2A p.Ala669Glu Uncertain significance ★★ ⚠ same condition
CC2D2A p.Arg1028Gln Uncertain significance ★★ same condition
CC2D2A p.Arg1028Trp Uncertain significance ★★ same condition
CC2D2A p.Arg1168His Uncertain significance ★★ ⚠ same condition
CC2D2A p.Arg1177His 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/cc2d2a-p-pro301arg (accessed [today's date]).

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