Is CD59 p.Val42fs (c.123del) pathogenic?

CD59 p.Val42fs (c.123del) is classified Pathogenic in CD59 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-01-03). Absent from gnomAD; Associated with primary CD59 deficiency.

What condition is associated with CD59 p.Val42fs (c.123del)?

CD59 p.Val42fs (c.123del) is associated with primary CD59 deficiency (ClinVar).

How common is CD59 p.Val42fs (c.123del) in the general population?

CD59 p.Val42fs (c.123del) is absent from gnomAD (gnomAD).

How is Primary CD59 deficiency inherited?

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

CD59 p.Val42fs

c.123del · rs2133545024 · VCV18052

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

primary CD59 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 within the last 50 nt of the penultimate exon (3 of 4, 46 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -15	GERP -3.1

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: CD59
Protein: p.Val42fs
Coding: c.123del
MANE Select: NM_000611
dbSNP: rs2133545024
Type: Deletion
Location: chr11:33717416 (GRCh38)
Gene constraint: LOEUF 1.277 · pLI 0.57 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.15 · 17 PDB
Residue 42: the upar/ly6 domain; a β-strand; a disulfide bond

Full CD59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary CD59 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary CD59 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CD59 p.Val42= Benign ★★ same residue
CD59 p.Asp47_Phe48insTer Likely pathogenic ★ same condition
CD59 p.Cys64fs Likely pathogenic ★ same condition
CD59 p.Glu101fs Likely pathogenic ★ same condition
CD59 p.Leu93_Cys94insTer Likely pathogenic ★ same condition
CD59 p.Phe96fs Uncertain significance ★ same condition
CD59 p.Val42Ile Uncertain significance ★ ⚠ same residue
CD59 p.Asp49fs 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/cd59-p-val42fs (accessed [today's date]).

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