Is C1S p.Asp577fs (c.1729_1730del) pathogenic?

C1S p.Asp577fs (c.17291730del) is classified Likely pathogenic in C1S (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). No gnomAD frequency available for this variant; Associated with complement component C1s deficiency.

What condition is associated with C1S p.Asp577fs (c.1729_1730del)?

C1S p.Asp577fs (c.1729_1730del) is associated with complement component C1s deficiency (ClinVar).

How common is C1S p.Asp577fs (c.1729_1730del) in the general population?

C1S p.Asp577fs (c.1729_1730del) is no gnomAD frequency available for this variant (gnomAD).

C1S p.Asp577fs

Q: How is Immunodeficiency due to a classical component pathway complement deficiency inherited?

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

c.1729_1730del · rs2539608457 · VCV1705563

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

complement component C1s 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	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.9	GERP -3.6

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: C1S
Protein: p.Asp577fs
Coding: c.1729_1730del
MANE Select: NM_001734
dbSNP: rs2539608457
Type: Microsatellite
Location: chr12:7070308 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.02 · 14 PDB
Residue 577: a β-strand; the peptidase s1 domain

Full C1S gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component C1s deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a classical component pathway complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C1S p.Arg437fs Pathogenic/Likely pathogenic ★★ same condition
C1S p.Phe378fs Pathogenic same condition
C1S p.Arg523Ter Pathogenic ★★ same condition
C1S p.Ser115fs Pathogenic ★★ same condition
C1S p.Arg245Trp Uncertain significance ★★ ⚠ same condition
C1S p.Arg331Cys Uncertain significance ★★ ⚠ same condition
C1S p.Arg534Trp Uncertain significance ★★ ⚠ same condition
C1S p.Gly172Arg Uncertain significance ★★ 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/c1s-p-asp577fs (accessed [today's date]).

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