Is C2CD3 p.Arg1115= (c.3345A>G) pathogenic?

C2CD3 p.Arg1115= (c.3345A>G) is classified Conflicting classifications of pathogenicity in C2CD3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-10). Ultra-rare (popmax 0.0119%, amr); Associated with Inborn genetic diseases.

What condition is associated with C2CD3 p.Arg1115= (c.3345A>G)?

C2CD3 p.Arg1115= (c.3345A>G) is associated with Inborn genetic diseases (ClinVar).

How common is C2CD3 p.Arg1115= (c.3345A>G) in the general population?

C2CD3 p.Arg1115= (c.3345A>G) is ultra-rare (popmax 0.0119%, amr) (gnomAD).

C2CD3 p.Arg1115=

c.3345A>G · rs141518273 · VCV2192595

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, amr)

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 -1	GERP -2, phastCons 0.005
Overall
CADD	7.814	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0119% Admixed American · 7/58,956 alleles

Filtering AF 0.00938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00882%

Overall 0.0087% 140/1,608,704 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0119%	8,422
European (non-Finnish)	0.011%	9,124
Remaining individualsnot grpmax-eligible	0.00643%	15,561

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: C2CD3
Protein: p.Arg1115=
Coding: c.3345A>G
MANE Select: NM_001286577
dbSNP: rs141518273
Type: single nucleotide variant
Location: chr11:74092588 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 1115: the c2 3 domain

Full C2CD3 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

C2CD3 c.2085+5G>A Uncertain significance ★★ same condition
C2CD3 c.4951+6C>T Uncertain significance ★★ same condition
C2CD3 p.Ala1382Pro Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala1777Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala95Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1122Ile Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1145His Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1183His 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/c2cd3-p-arg1115 (accessed [today's date]).

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