Is CD55 p.Arg52Leu (c.155G>T) pathogenic?

CD55 p.Arg52Leu (c.155G>T) is classified Benign/Likely benign in CD55 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1408); Low-frequency (popmax 2.61%, afr); Associated with protein-losing enteropathy.

What condition is associated with CD55 p.Arg52Leu (c.155G>T)?

CD55 p.Arg52Leu (c.155G>T) is associated with protein-losing enteropathy (ClinVar).

How common is CD55 p.Arg52Leu (c.155G>T) in the general population?

CD55 p.Arg52Leu (c.155G>T) is low-frequency (popmax 2.61%, afr) (gnomAD).

What do computational predictors say about CD55 p.Arg52Leu (c.155G>T)?

AlphaMissense predicts likely benign (score 0.1408) — an in-silico prediction, not a clinical call.

CD55 p.Arg52Leu

Q: How is Complement hyperactivation-angiopathic thrombosis-protein-losing enteropathy syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.155G>T · rs28371588 · VCV787220

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1408 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.61%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

protein-losing enteropathy

Computational evidence

Protein change
AlphaMissense	0.1408	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.84	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 -10	GERP -2.9
Regional constraint	o/e 1.17	unconstrained · MANE · 761 bp · p 0.08 · regional, not allelic
Overall
CADD	0.001	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 2.61% African / African-American · 1,962/75,054 alleles

Filtering AF 2.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.48%

Overall 0.135% 2,185/1,614,142 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.61%	38
Admixed American	0.168%	594
Remaining individualsnot grpmax-eligible	0.154%	651
Middle Eastern	0.099%	1,010
South Asian	0.00549%	18,218
European (non-Finnish)	0.00127%	78,664

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: CD55
Protein: p.Arg52Leu
Coding: c.155G>T
MANE Select: NM_000574
dbSNP: rs28371588
Type: single nucleotide variant
Location: chr1:207322436 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 52: a disulfide bond; a UniProt-annotated variant site (in tc(b) antigen); a UniProt-annotated variant site (in tc(c) antigen); the sushi 1 domain

Full CD55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

protein-losing enteropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Complement hyperactivation-angiopathic thrombosis-protein-losing enteropathy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

CD55 p.Arg52Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CD55 c.286+2T>G Likely pathogenic ★★ same condition
CD55 p.Glu50Ter Pathogenic/Likely pathogenic ★★ same condition
CD55 c.1081+1G>C Uncertain significance ★★ same condition
CD55 p.Arg357Cys Uncertain significance ★★ ⚠ same condition
CD55 p.Cys267Ser Pathogenic ★ same condition
CD55 p.Ser199Leu Pathogenic ★ ⚠ same condition
CD55 p.Trp33Ter Pathogenic ★ same condition

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/cd55-p-arg52leu (accessed [today's date]).

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