Is CD59 p.Phe96Leu (c.288T>G) pathogenic?

CD59 p.Phe96Leu (c.288T>G) is classified Uncertain significance in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). AlphaMissense: ambiguous (0.5164); Absent from gnomAD v4.1.

How common is CD59 p.Phe96Leu (c.288T>G) in the general population?

CD59 p.Phe96Leu (c.288T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD59 p.Phe96Leu (c.288T>G)?

AlphaMissense predicts ambiguous (score 0.5164) — an in-silico prediction, not a clinical call.

CD59 p.Phe96Leu

c.288T>G · rs200170584 · VCV1354058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5164 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5164	ambiguous
REVEL	0.056	moderately benign-leaning
SaProt	LLR -4.97	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	0.019	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

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.Phe96Leu
Coding: c.288T>G
MANE Select: NM_000611
dbSNP: rs200170584
Type: single nucleotide variant
Location: chr11:33710225 (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 96: the upar/ly6 domain

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

Similar variants

CD59 p.Phe96= Likely benign ★ same residue
CD59 p.Phe96fs Uncertain significance ★ 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-phe96leu (accessed [today's date]).

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