Is CD59 p.Cys64Gly (c.190T>G) pathogenic?

CD59 p.Cys64Gly (c.190T>G) is classified Uncertain significance in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-03). AlphaMissense: likely pathogenic (0.9345); Absent from gnomAD v4.1; Associated with primary CD59 deficiency.

What condition is associated with CD59 p.Cys64Gly (c.190T>G)?

CD59 p.Cys64Gly (c.190T>G) is associated with primary CD59 deficiency (ClinVar).

How common is CD59 p.Cys64Gly (c.190T>G) in the general population?

CD59 p.Cys64Gly (c.190T>G) is absent from gnomAD v4.1 (gnomAD).

How is Primary CD59 deficiency inherited?

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

What do computational predictors say about CD59 p.Cys64Gly (c.190T>G)?

AlphaMissense predicts likely pathogenic (score 0.9345) — an in-silico prediction, not a clinical call.

CD59 p.Cys64Gly

c.190T>G · rs1554939509 · VCV522723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9345 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary CD59 deficiency

Computational evidence

Protein change
AlphaMissense	0.9345	likely pathogenic · top 10% in CD59
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -9.99	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD59
Protein: p.Cys64Gly
Coding: c.190T>G
MANE Select: NM_000611
dbSNP: rs1554939509
Type: single nucleotide variant
Location: chr11:33710323 (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 64: a disulfide bond; the upar/ly6 domain; a β-strand

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.Cys64fs Likely pathogenic ★ same residue
CD59 p.Cys89Tyr Pathogenic ★★ same condition
CD59 p.Met1Thr Likely pathogenic ★★ same condition
CD59 p.Asp49Val Pathogenic ★ same condition
CD59 p.Cys28Tyr Conflicting classifications of pathogenicity ★ same condition
CD59 p.Tyr29Asp Uncertain significance ★ ⚠ same condition
CD59 p.Asp47_Phe48insTer Likely pathogenic ★ same condition
CD59 p.Glu101fs 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/cd59-p-cys64gly (accessed [today's date]).

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