Is CD59 p.Ala50Val (c.149C>T) pathogenic?

CD59 p.Ala50Val (c.149C>T) is classified Uncertain significance in CD59 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-20). AlphaMissense: likely benign (0.1235); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with CD59 p.Ala50Val (c.149C>T)?

CD59 p.Ala50Val (c.149C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD59 p.Ala50Val (c.149C>T) in the general population?

CD59 p.Ala50Val (c.149C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CD59 p.Ala50Val (c.149C>T)?

AlphaMissense predicts likely benign (score 0.1235) — an in-silico prediction, not a clinical call.

CD59 p.Ala50Val

c.149C>T · rs759088791 · VCV1399706

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1235 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1235	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -9.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -2.6, phastCons 0.87
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	12.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00534% African / African-American · 4/74,852 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00211% 34/1,611,416 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
Admixed American	0.005%	19,994
European (non-Finnish)	0.00221%	45,297
Remaining individualsnot grpmax-eligible	0.0016%	62,400

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.Ala50Val
Coding: c.149C>T
MANE Select: NM_000611
dbSNP: rs759088791
Type: single nucleotide variant
Location: chr11:33717390 (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 50: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD59 p.Ala50= Benign/Likely benign ★★ same residue
CD59 p.Asn33Thr Uncertain significance ★★ ⚠ same condition
CD59 p.Asp92Asn Uncertain significance ★★ ⚠ same condition
CD59 p.Thr105Pro Uncertain significance ★★ ⚠ same condition
CD59 p.Asn43Ser Uncertain significance ★ ⚠ same condition
CD59 p.Glu81Lys Uncertain significance ★ ⚠ same condition
CD59 p.His24Arg Uncertain significance ★ ⚠ same condition
CD59 p.Val15Ile Conflicting classifications of pathogenicity ★ ⚠ 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-ala50val (accessed [today's date]).

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