Is CC2D1A p.Arg629Pro (c.1886G>C) pathogenic?

CC2D1A p.Arg629Pro (c.1886G>C) is classified Uncertain significance in CC2D1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: ambiguous (0.4836); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Arg629Pro (c.1886G>C)?

CC2D1A p.Arg629Pro (c.1886G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D1A p.Arg629Pro (c.1886G>C) in the general population?

CC2D1A p.Arg629Pro (c.1886G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D1A p.Arg629Pro (c.1886G>C)?

AlphaMissense predicts ambiguous (score 0.4836) — an in-silico prediction, not a clinical call.

CC2D1A p.Arg629Pro

c.1886G>C · VCV4220131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4836 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4836	ambiguous
REVEL	0.124	moderately benign-leaning
SaProt	LLR -12.69	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP -0.49, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	23.1	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

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: CC2D1A
Protein: p.Arg629Pro
Coding: c.1886G>C
MANE Select: NM_017721
Type: single nucleotide variant
Location: chr19:13923757 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB

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.Arg629Gln Uncertain significance ★ ⚠ same residue
CC2D1A p.Arg629Trp 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
CC2D1A p.Ala481Val 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-arg629pro (accessed [today's date]).

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