Is CD59 p.Asp49fs (c.146del) pathogenic?

CD59 p.Asp49fs (c.146del) is classified Pathogenic in CD59 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-01-02). Very rare (popmax 8.48e-05%, nfe); Associated with primary CD59 deficiency.

What condition is associated with CD59 p.Asp49fs (c.146del)?

CD59 p.Asp49fs (c.146del) is associated with primary CD59 deficiency (ClinVar).

How common is CD59 p.Asp49fs (c.146del) in the general population?

CD59 p.Asp49fs (c.146del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Primary CD59 deficiency inherited?

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

CD59 p.Asp49fs

c.146del · rs587777149 · VCV100766

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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, 23 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 0.021	GERP -0.58

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,114 alleles

Overall 6.2e-05% 1/1,613,150 alleles · very rare exomes 1/1,460,828 · genomes 0/152,322 · joint denominator

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: CD59
Protein: p.Asp49fs
Coding: c.146del
MANE Select: NM_000611
dbSNP: rs587777149
Type: Deletion
Location: chr11:33717393 (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 49: the upar/ly6 domain

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.Asp49Val Pathogenic ★ 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.Val42fs Pathogenic same condition
CD59 p.Cys89Tyr 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-asp49fs (accessed [today's date]).

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