Is CD59 p.Glu101Ala (c.302A>C) pathogenic?

CD59 p.Glu101Ala (c.302A>C) is classified Uncertain significance in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.1137); Absent from gnomAD v4.1.

How common is CD59 p.Glu101Ala (c.302A>C) in the general population?

CD59 p.Glu101Ala (c.302A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD59 p.Glu101Ala (c.302A>C)?

AlphaMissense predicts likely benign (score 0.1137) — an in-silico prediction, not a clinical call.

CD59 p.Glu101Ala

c.302A>C · rs2495426559 · VCV1999350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1137 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1137	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.06	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 -3.5	GERP -2.7
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	0.744	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.Glu101Ala
Coding: c.302A>C
MANE Select: NM_000611
dbSNP: rs2495426559
Type: single nucleotide variant
Location: chr11:33710211 (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 101: the upar/ly6 domain

Full CD59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD59 p.Glu101Lys Uncertain significance ★ ⚠ same residue
CD59 p.Glu101fs Likely pathogenic ★ same residue
CD59 p.Cys89Tyr Pathogenic ★★ same type
CD59 p.Met1Thr Likely pathogenic ★★ same type
CD59 p.Ala50Val Uncertain significance ★★ ⚠ same type
CD59 p.Arg78Cys Uncertain significance ★★ ⚠ same type
CD59 p.Asn33Thr Uncertain significance ★★ ⚠ same type
CD59 p.Asp92Asn Uncertain significance ★★ ⚠ same type

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-glu101ala (accessed [today's date]).

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