Is CC2D1A p.Pro209= (c.627T>C) pathogenic?

CC2D1A p.Pro209= (c.627T>C) is classified Likely benign in CC2D1A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-01). Ultra-rare (popmax 0.0173%, afr); Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Pro209= (c.627T>C)?

CC2D1A p.Pro209= (c.627T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D1A p.Pro209= (c.627T>C) in the general population?

CC2D1A p.Pro209= (c.627T>C) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

CC2D1A p.Pro209=

c.627T>C · rs753037271 · VCV589551

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.6	GERP -4.6
Overall
CADD	0.488	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/74,946 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00112% 18/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,765
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Admixed American	0.00333%	30,001

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.Pro209=
Coding: c.627T>C
MANE Select: NM_017721
dbSNP: rs753037271
Type: single nucleotide variant
Location: chr19:13913517 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 209: 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 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
CC2D1A p.Ala507Val Uncertain significance ★★ ⚠ same condition
CC2D1A p.Ala50Ser 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-pro209 (accessed [today's date]).

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