Is CC2D1A p.Pro314fs (c.938dup) pathogenic?

CC2D1A p.Pro314fs (c.938dup) is classified Pathogenic/Likely pathogenic in CC2D1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-14). Very rare (popmax 0.000254%, nfe); Associated with CC2D1A-related disorder.

What condition is associated with CC2D1A p.Pro314fs (c.938dup)?

CC2D1A p.Pro314fs (c.938dup) is associated with CC2D1A-related disorder (ClinVar).

How common is CC2D1A p.Pro314fs (c.938dup) in the general population?

CC2D1A p.Pro314fs (c.938dup) is very rare (popmax 0.000254%, nfe) (gnomAD).

CC2D1A p.Pro314fs

c.938dup · rs750222217 · VCV2752522

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

CC2D1A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -0.017, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,936 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,362 alleles · very rare

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.Pro314fs
Coding: c.938dup
MANE Select: NM_017721
dbSNP: rs750222217
Type: Duplication
Location: chr19:13918563 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 314: the 'disordered' region

Full CC2D1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CC2D1A-related disorder

Similar variants

CC2D1A p.Lys116fs Pathogenic ★★ same condition
CC2D1A p.Arg886His Conflicting classifications of pathogenicity ★ ⚠ same condition
CC2D1A p.Thr580Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
CC2D1A p.Arg355fs Pathogenic/Likely pathogenic ★★ same type
CC2D1A p.Arg155_Ala161dup Uncertain significance ★★ same type
CC2D1A c.2454+12dup Benign ★★ same type
CC2D1A p.Arg783fs Likely pathogenic ★ same type
CC2D1A p.Asp321fs Likely pathogenic ★ same type

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-pro314fs (accessed [today's date]).

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