Is C3 c.682+6AGG[2] pathogenic?

C3 c.682+6AGG[2] is classified Likely benign in C3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). Very rare (popmax 0.00333%, amr).

How common is C3 c.682+6AGG[2] in the general population?

C3 c.682+6AGG[2] is very rare (popmax 0.00333%, amr) (gnomAD).

C3 c.682+6AGG[2]

rs1568227060 · VCV2793937

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
Splice region	donor +6	donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,988 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,150 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: C3
Coding: c.682+6AGG[2]
MANE Select: NM_000064
dbSNP: rs1568227060
Type: Microsatellite
Location: chr19:6714152 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB

Full C3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C3 p.Val942fs Pathogenic/Likely pathogenic ★★ same type
C3 c.1686+48TC[8] Benign ★★ same type
C3 c.1976-28TCT[2] Likely benign ★★ same type
C3 c.2048-14_2048-13del Benign/Likely benign ★★ same type
C3 c.2951-5_2951-3del Conflicting classifications of pathogenicity ★ same type
C3 c.3155-17CT[3] Conflicting classifications of pathogenicity ★ same type
C3 p.Arg736_Gln737insArg Uncertain significance ★ same type
C3 p.Asn1137del 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/c3-c-682-plus-6agg-2 (accessed [today's date]).

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