Is C6 p.Lys768fs (c.2304del) pathogenic?

C6 p.Lys768fs (c.2304del) is classified Pathogenic in C6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). Very rare (popmax 0.00133%, afr).

How common is C6 p.Lys768fs (c.2304del) in the general population?

C6 p.Lys768fs (c.2304del) is very rare (popmax 0.00133%, afr) (gnomAD).

C6 p.Lys768fs

c.2304del · rs1468759946 · VCV2800265

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 16 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.18	GERP 0.15

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,932 alleles

Overall 6.86e-05% 1/1,458,274 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: C6
Protein: p.Lys768fs
Coding: c.2304del
MANE Select: NM_000065
dbSNP: rs1468759946
Type: Deletion
Location: chr5:41150012 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 768: the 'c5b-binding domain' region; the 'factor i module (fim) 1' region

Full C6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C6 p.Gln274fs Pathogenic/Likely pathogenic ★★ same type
C6 p.Gln380fs Pathogenic/Likely pathogenic ★★ same type
C6 p.Gln779fs Pathogenic/Likely pathogenic ★★ same type
C6 p.Ser813fs Pathogenic/Likely pathogenic ★★ same type
C6 p.Asp696fs Pathogenic ★ same type
C6 p.Cys539fs Pathogenic ★ same type
C6 p.Cys837_Asp839delinsTer Likely pathogenic ★ same type
C6 p.Glu417fs 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/c6-p-lys768fs (accessed [today's date]).

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