Is C1S p.Asn642fs (c.1923dup) pathogenic?

C1S p.Asn642fs (c.1923dup) is classified Uncertain significance in C1S (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-20). Absent from gnomAD.

How common is C1S p.Asn642fs (c.1923dup) in the general population?

C1S p.Asn642fs (c.1923dup) is absent from gnomAD (gnomAD).

C1S p.Asn642fs

c.1923dup · rs1185285395 · VCV2770367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -0.33	GERP -3.7

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.Asn642fs
Coding: c.1923dup
MANE Select: NM_001734
dbSNP: rs1185285395
Type: Duplication
Location: chr12:7070504 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.02 · 14 PDB
Residue 642: a disulfide bond; the peptidase s1 domain

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

Similar variants

C1S p.Asn642Asp Uncertain significance ★★ ⚠ same residue
C1S p.Asn642Lys Uncertain significance ★ ⚠ same residue
C1S p.Asp178fs Pathogenic ★ same type
C1S p.Asp269fs Pathogenic ★ same type
C1S p.Leu82fs Pathogenic ★ same type
C1S p.Arg686fs Uncertain significance ★ same type
C1S p.Asp673delinsGlyTer Uncertain significance ★ same type
C1S p.Lys623fs 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/c1s-p-asn642fs (accessed [today's date]).

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