Is CD59 p.Pro128Ser (c.382C>T) pathogenic?

CD59 p.Pro128Ser (c.382C>T) is classified Uncertain significance in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.1195); Ultra-rare (popmax 0.0329%, mid).

How common is CD59 p.Pro128Ser (c.382C>T) in the general population?

CD59 p.Pro128Ser (c.382C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CD59 p.Pro128Ser (c.382C>T)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

CD59 p.Pro128Ser

c.382C>T · rs369200735 · VCV1046649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -5.66	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 0.73	GERP -3.1, phastCons 0.018
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.52 · regional, not allelic
Overall
CADD	15.41	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 0.0329% Middle Eastern · 2/6,078 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00403% 65/1,611,598 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
Remaining individualsnot grpmax-eligible	0.00962%	10,396
European (non-Finnish)	0.0045%	22,236
African / African-American	0.00267%	37,447
Admixed American	0.00167%	59,746
South Asian	0.0011%	90,738

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.Pro128Ser
Coding: c.382C>T
MANE Select: NM_000611
dbSNP: rs369200735
Type: single nucleotide variant
Location: chr11:33710131 (GRCh38)
Gene constraint: LOEUF 1.277 · pLI 0.57 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.15 · 17 PDB

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

Similar variants

CD59 p.Pro128= Likely benign ★ 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
CD59 p.Thr105Pro 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-pro128ser (accessed [today's date]).

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