Is CD55 p.Arg357Cys (c.1069C>T) pathogenic?

CD55 p.Arg357Cys (c.1069C>T) is classified Uncertain significance in CD55 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-07-07). AlphaMissense: likely benign (0.1825); Very rare (popmax 0.00559%, sas); Associated with protein-losing enteropathy.

What condition is associated with CD55 p.Arg357Cys (c.1069C>T)?

CD55 p.Arg357Cys (c.1069C>T) is associated with protein-losing enteropathy (ClinVar).

How common is CD55 p.Arg357Cys (c.1069C>T) in the general population?

CD55 p.Arg357Cys (c.1069C>T) is very rare (popmax 0.00559%, sas) (gnomAD).

What do computational predictors say about CD55 p.Arg357Cys (c.1069C>T)?

AlphaMissense predicts likely benign (score 0.1825) — an in-silico prediction, not a clinical call.

CD55 p.Arg357Cys

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.1069C>T · rs778188153 · VCV1942790

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00559%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

protein-losing enteropathy

Computational evidence

Protein change
AlphaMissense	0.1825	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -8.66	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 -1.4	GERP -2.9
Regional constraint	o/e 0.90	unconstrained · MANE · 33 kb · p 0.17 · regional, not allelic
Overall
CADD	0.144	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 0.00559% South Asian · 5/89,440 alleles

Filtering AF 0.00284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00405% 65/1,605,198 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0157%	6,373
South Asiangrpmax	0.00559%	17,888
East Asian	0.0045%	22,225
European (non-Finnish)	0.00374%	26,735
Admixed American	0.00343%	29,156
Remaining individualsnot grpmax-eligible	0.00161%	62,040
African / African-American	0.00134%	74,474

Finnish 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: CD55
Protein: p.Arg357Cys
Coding: c.1069C>T
MANE Select: NM_000574
dbSNP: rs778188153
Type: single nucleotide variant
Location: chr1:207339405 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB

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.Arg357His Uncertain significance ★★ ⚠ 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.Arg52Leu Benign/Likely benign ★★ ⚠ 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-arg357cys (accessed [today's date]).

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