Is CD59 p.Glu81Lys (c.241G>A) pathogenic?

CD59 p.Glu81Lys (c.241G>A) is classified Uncertain significance in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.2756); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CD59 p.Glu81Lys (c.241G>A)?

CD59 p.Glu81Lys (c.241G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CD59 p.Glu81Lys (c.241G>A) in the general population?

CD59 p.Glu81Lys (c.241G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD59 p.Glu81Lys (c.241G>A)?

AlphaMissense predicts likely benign (score 0.2756) — an in-silico prediction, not a clinical call.

CD59 p.Glu81Lys

c.241G>A · VCV4608009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2756 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2756	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.29	GERP 0.56
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	16.5	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

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.Glu81Lys
Coding: c.241G>A
MANE Select: NM_000611
Type: single nucleotide variant
Location: chr11:33710272 (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 81: a disulfide bond; the upar/ly6 domain

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.Glu81= Likely benign ★ same residue
CD59 p.Ala50Val Uncertain significance ★★ ⚠ same condition
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.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-glu81lys (accessed [today's date]).

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