Is C6 p.Cys543fs (c.1628_1629del) pathogenic?

C6 p.Cys543fs (c.16281629del) is classified Likely pathogenic in C6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). Absent from gnomAD v4.1; Associated with complement component 6 deficiency.

What condition is associated with C6 p.Cys543fs (c.1628_1629del)?

C6 p.Cys543fs (c.1628_1629del) is associated with complement component 6 deficiency (ClinVar).

How common is C6 p.Cys543fs (c.1628_1629del) in the general population?

C6 p.Cys543fs (c.1628_1629del) is absent from gnomAD v4.1 (gnomAD).

C6 p.Cys543fs

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1628_1629del · VCV3592690

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,478)

Conditions

complement component 6 deficiency

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 11 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,478). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C6
Protein: p.Cys543fs
Coding: c.1628_1629del
MANE Select: NM_000065
Type: Microsatellite
Location: chr5:41160197 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 543: a disulfide bond; the egf-like domain

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

Disease context

complement component 6 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C6 p.Gln544fs Pathogenic/Likely pathogenic ★★ same condition
C6 p.Val802_Phe803insTer Pathogenic/Likely pathogenic ★★ same condition
C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Arg606Ter Pathogenic ★★ same condition
C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Gln274fs Pathogenic/Likely pathogenic ★★ same condition
C6 p.Gln380fs Pathogenic/Likely pathogenic ★★ same condition
C6 p.Gln779fs Pathogenic/Likely pathogenic ★★ 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/c6-p-cys543fs (accessed [today's date]).

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