Is C2CD3 c.955+11A>G pathogenic?

C2CD3 c.955+11A>G is classified Benign in C2CD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.25%, nfe).

How common is C2CD3 c.955+11A>G in the general population?

C2CD3 c.955+11A>G is low-frequency (popmax 1.25%, nfe) (gnomAD).

C2CD3 c.955+11A>G

rs3915257 · VCV1583232

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +11	near-intronic (+11 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.79	GERP -3.5
Non-coding constraint	Z 1.30	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	1.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.25% European (non-Finnish) · 14,695/1,175,278 alleles

Filtering AF 1.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.23%

Overall 1.05% 16,970/1,608,664 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.5%	22
Ashkenazi Jewishnot grpmax-eligible	1.94%	51
European (non-Finnish)grpmax	1.25%	80
Remaining individualsnot grpmax-eligible	1.03%	97
Finnishnot grpmax-eligible	0.549%	182
Middle Eastern	0.496%	202
Admixed American	0.46%	217
South Asian	0.229%	437
African / African-American	0.199%	503
East Asian	0.00223%	44,854

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.955+11A>G
MANE Select: NM_001286577
dbSNP: rs3915257
Type: single nucleotide variant
Location: chr11:74138709 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65

Full C2CD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD3 c.3911-2A>T Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg621Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg666Ter Pathogenic ★★ same type
C2CD3 p.Arg768Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Tyr173Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 c.2085+5G>A Uncertain significance ★★ same type
C2CD3 c.4951+6C>T Uncertain significance ★★ same type
C2CD3 c.5495+4A>G Uncertain significance ★★ 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/c2cd3-c-955-plus-11a-g (accessed [today's date]).

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