Is CD52 p.Cys59Tyr (c.176G>A) pathogenic?

CD52 p.Cys59Tyr (c.176G>A) is classified Likely benign in CD52 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.0905); Ultra-rare (popmax 0.0165%, mid).

How common is CD52 p.Cys59Tyr (c.176G>A) in the general population?

CD52 p.Cys59Tyr (c.176G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD52 p.Cys59Tyr (c.176G>A)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

CD52 p.Cys59Tyr

c.176G>A · rs41285429 · VCV2335104

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -2.74	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 0.97	GERP -3.2
Regional constraint	o/e 0.82	unconstrained · MANE · 2,281 bp · p 0.11 · regional, not allelic
Overall
CADD	5.984	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

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00422% 68/1,611,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
European (non-Finnish)	0.00534%	18,719
Remaining individualsnot grpmax-eligible	0.00481%	20,799
African / African-American	0.00134%	74,720

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: CD52
Protein: p.Cys59Tyr
Coding: c.176G>A
MANE Select: NM_001803
dbSNP: rs41285429
Type: single nucleotide variant
Location: chr1:26320292 (GRCh38)
Gene constraint: LOEUF 1.787 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 68.22 · 1 PDB

Full CD52 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD52 p.Cys59Gly Uncertain significance ★ ⚠ same residue
CD52 p.Arg3Cys Uncertain significance ★ ⚠ same type
CD52 p.Gly43Arg Uncertain significance ★ ⚠ same type
CD52 p.Ile11Val Uncertain significance ★ ⚠ same type
CD52 p.Leu5Val Uncertain significance ★ ⚠ same type
CD52 p.Met16Thr Uncertain significance ★ ⚠ same type
CD52 p.Val15Leu Uncertain significance ★ ⚠ same type
CD52 p.Val17Leu 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/cd52-p-cys59tyr (accessed [today's date]).

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