Is CD59 p.Asp49Val (c.146A>T) pathogenic?

CD59 p.Asp49Val (c.146A>T) is classified Pathogenic in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-15). AlphaMissense: likely pathogenic (0.9522); Very rare (popmax 8.48e-05%, nfe); Associated with primary CD59 deficiency.

What condition is associated with CD59 p.Asp49Val (c.146A>T)?

CD59 p.Asp49Val (c.146A>T) is associated with primary CD59 deficiency (ClinVar).

How common is CD59 p.Asp49Val (c.146A>T) in the general population?

CD59 p.Asp49Val (c.146A>T) 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.

What do computational predictors say about CD59 p.Asp49Val (c.146A>T)?

AlphaMissense predicts likely pathogenic (score 0.9522) — an in-silico prediction, not a clinical call.

CD59 p.Asp49Val

c.146A>T · VCV4848546

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9522 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary CD59 deficiency

Computational evidence

Protein change
AlphaMissense	0.9522	likely pathogenic ✓ concordant with ClinVar · top 9% in CD59
REVEL	0.703	pathogenic-leaning
SaProt	LLR -13.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.1	GERP 1.7, phastCons 0.97
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,156 alleles

Overall 6.85e-05% 1/1,460,888 alleles · very rare

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.Asp49Val
Coding: c.146A>T
MANE Select: NM_000611
Type: single nucleotide variant
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: a disulfide bond; 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.Asp49fs Pathogenic same residue
CD59 p.Cys89Tyr Pathogenic ★★ same condition
CD59 p.Met1Thr Likely pathogenic ★★ same condition
CD59 p.Cys28Tyr Conflicting classifications of pathogenicity ★ same condition
CD59 p.Cys64Gly Uncertain significance ★ ⚠ same condition
CD59 p.Tyr29Asp Uncertain significance ★ ⚠ same condition
CD59 p.Asp47_Phe48insTer Likely pathogenic ★ same condition
CD59 p.Cys64fs 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-asp49val (accessed [today's date]).

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