Is C5 p.Cys27fs (c.79del) pathogenic?

C5 p.Cys27fs (c.79del) is classified Likely pathogenic in C5 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.000442%, nfe).

How common is C5 p.Cys27fs (c.79del) in the general population?

C5 p.Cys27fs (c.79del) is very rare (popmax 0.000442%, nfe) (gnomAD).

C5 p.Cys27fs

c.79del · rs1362872776 · VCV1049860

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000442%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.005	GERP 0.94

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000442% European (non-Finnish) · 1/226,390 alleles

Overall 0.000332% 1/301,028 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: C5
Protein: p.Cys27fs
Coding: c.79del
MANE Select: NM_001735 · reported on NM_001317163
dbSNP: rs1362872776
Type: Deletion
Location: chr9:121074758 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 27: a UniProt-annotated variant site (in c5d)

Full C5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C5 c.3154+13del Benign/Likely benign ★★ same type
C5 c.4220+20_4220+27del Likely benign ★★ same type
C5 p.Ala1155fs Likely pathogenic ★ same type
C5 p.Gln1504fs Pathogenic ★ same type
C5 p.Glu1413fs Pathogenic ★ same type
C5 p.His1390fs Pathogenic ★ same type
C5 p.Ile509fs Pathogenic ★ same type
C5 p.Leu1161fs 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/c5-p-cys27fs (accessed [today's date]).

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