Is CD55 p.Glu50Ter (c.148G>T) pathogenic?

CD55 p.Glu50Ter (c.148G>T) is classified Pathogenic/Likely pathogenic in CD55 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). Very rare (popmax 0.00988%, sas); Associated with protein-losing enteropathy.

What condition is associated with CD55 p.Glu50Ter (c.148G>T)?

CD55 p.Glu50Ter (c.148G>T) is associated with protein-losing enteropathy (ClinVar).

How common is CD55 p.Glu50Ter (c.148G>T) in the general population?

CD55 p.Glu50Ter (c.148G>T) is very rare (popmax 0.00988%, sas) (gnomAD).

CD55 p.Glu50Ter

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.148G>T · rs773074921 · VCV3064847

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

protein-losing enteropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 10
REVEL	0.004	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -3
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,090 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000684% 10/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,121
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Glu50Ter
Coding: c.148G>T
MANE Select: NM_000574
dbSNP: rs773074921
Type: single nucleotide variant
Location: chr1:207322429 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 50: a disulfide bond; 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.Glu50Lys Uncertain significance ★ ⚠ same residue
CD55 p.Glu50fs Pathogenic same residue
CD55 c.286+2T>G Likely pathogenic ★★ same condition
CD55 c.1081+1G>C Uncertain significance ★★ same condition
CD55 p.Arg357Cys Uncertain significance ★★ ⚠ same condition
CD55 p.Arg52Leu Benign/Likely benign ★★ ⚠ same condition
CD55 p.Cys267Ser Pathogenic ★ same condition
CD55 p.Ser199Leu 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-glu50ter (accessed [today's date]).

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