Is CD55 p.Ser199Leu (c.596C>T) pathogenic?

CD55 p.Ser199Leu (c.596C>T) is classified Pathogenic in CD55 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-05). AlphaMissense: likely benign (0.1968); Ultra-rare (popmax 0.0164%, mid); Associated with protein-losing enteropathy.

What condition is associated with CD55 p.Ser199Leu (c.596C>T)?

CD55 p.Ser199Leu (c.596C>T) is associated with protein-losing enteropathy (ClinVar).

How common is CD55 p.Ser199Leu (c.596C>T) in the general population?

CD55 p.Ser199Leu (c.596C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CD55 p.Ser199Leu (c.596C>T)?

AlphaMissense predicts likely benign (score 0.1968) — an in-silico prediction, not a clinical call.

CD55 p.Ser199Leu

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.596C>T · rs1135402914 · VCV431759

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1968 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

protein-losing enteropathy

Computational evidence

Protein change
AlphaMissense	0.1968	likely benign ⚠ discordant with ClinVar
REVEL	0.195	benign-leaning
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.80	acceptor loss · deltas
Pangolin	Δ0.61	loss · gain 0.57 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -9.8	GERP -3.3
Regional constraint	o/e 0.68	unconstrained · MANE · 4,298 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	2.577	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,613,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00401%	24,952
South Asian	0.0011%	91,032
European (non-Finnish)	0.000254%	393,184

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.Ser199Leu
Coding: c.596C>T
MANE Select: NM_000574
dbSNP: rs1135402914
Type: single nucleotide variant
Location: chr1:207326769 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 199: a disulfide bond; a UniProt-annotated variant site (in dr(a-) antigen); the sushi 3 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 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.Arg52Leu Benign/Likely benign ★★ ⚠ same condition
CD55 p.Cys267Ser Pathogenic ★ same condition
CD55 p.Trp33Ter Pathogenic ★ same condition
CD55 p.Glu50Lys Uncertain significance ★ ⚠ 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-ser199leu (accessed [today's date]).

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