Is CD59 p.Tyr29Asp (c.85T>G) pathogenic?

CD59 p.Tyr29Asp (c.85T>G) is classified Uncertain significance in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely pathogenic (0.9596); Absent from gnomAD v4.1; Associated with primary CD59 deficiency.

What condition is associated with CD59 p.Tyr29Asp (c.85T>G)?

CD59 p.Tyr29Asp (c.85T>G) is associated with primary CD59 deficiency (ClinVar).

How common is CD59 p.Tyr29Asp (c.85T>G) in the general population?

CD59 p.Tyr29Asp (c.85T>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.Tyr29Asp (c.85T>G)?

AlphaMissense predicts likely pathogenic (score 0.9596) — an in-silico prediction, not a clinical call.

CD59 p.Tyr29Asp

c.85T>G · rs1564972905 · VCV634643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9596 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary CD59 deficiency

Computational evidence

Protein change
AlphaMissense	0.9596	likely pathogenic · top 8% in CD59
REVEL	0.584	indeterminate
SaProt	LLR -14.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.61, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Tyr29Asp
Coding: c.85T>G
MANE Select: NM_000611
dbSNP: rs1564972905
Type: single nucleotide variant
Location: chr11:33717454 (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 29: 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.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.Cys64Gly Uncertain significance ★ ⚠ same condition
CD59 p.Asp47_Phe48insTer Likely pathogenic ★ same condition
CD59 p.Cys64fs 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-tyr29asp (accessed [today's date]).

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