Is CD52 p.Asn40Ser (c.119A>G) pathogenic?

CD52 p.Asn40Ser (c.119A>G) is classified Benign in CD52 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-16). AlphaMissense: likely benign (0.0726); Common (popmax 76.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with CD52-related disorder.

What condition is associated with CD52 p.Asn40Ser (c.119A>G)?

CD52 p.Asn40Ser (c.119A>G) is associated with CD52-related disorder (ClinVar).

What do computational predictors say about CD52 p.Asn40Ser (c.119A>G)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

CD52 p.Asn40Ser

Q: How common is CD52 p.Asn40Ser (c.119A>G) in the general population?

CD52 p.Asn40Ser (c.119A>G) is common (popmax 76.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.119A>G · rs1071849 · VCV3059084

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 76.1%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD52-related disorder

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -4.00	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 0.4	GERP -3
Regional constraint	o/e 0.82	unconstrained · MANE · 2,281 bp · p 0.11 · regional, not allelic
Overall
CADD	3.87	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 76.1% European (non-Finnish) · 897,035/1,179,450 alleles

Filtering AF 75.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 75.9%

Overall 72.4% 1,167,023/1,612,364 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	80.7%	1
Ashkenazi Jewishnot grpmax-eligible	76.9%	1
European (non-Finnish)grpmax	76.1%	1
Finnishnot grpmax-eligible	70.7%	1
Middle Eastern	70.2%	1
Remaining individualsnot grpmax-eligible	70%	1
African / African-American	66%	2
Admixed American	59.9%	2
South Asian	54.4%	2
East Asian	42.3%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn40Ser
Coding: c.119A>G
MANE Select: NM_001803
dbSNP: rs1071849
Type: single nucleotide variant
Location: chr1:26320235 (GRCh38)
Gene constraint: LOEUF 1.787 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 68.22 · 1 PDB
Residue 40: a UniProt-annotated variant site (in)

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

Disease context

CD52-related disorder

Similar variants

CD52 p.Ile41Met Benign ⚠ same condition
CD52 p.Phe4= Likely benign same condition
CD52 p.Arg3Cys Uncertain significance ★ ⚠ same type
CD52 p.Cys59Gly 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

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-asn40ser (accessed [today's date]).

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