Is C5 p.Glu1011Asp (c.3033G>C) pathogenic?

C5 p.Glu1011Asp (c.3033G>C) is classified Benign/Likely benign in C5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely pathogenic (0.5832); Low-frequency (popmax 1.13%, afr); Associated with complement component 5 deficiency.

What condition is associated with C5 p.Glu1011Asp (c.3033G>C)?

C5 p.Glu1011Asp (c.3033G>C) is associated with complement component 5 deficiency (ClinVar).

How common is C5 p.Glu1011Asp (c.3033G>C) in the general population?

C5 p.Glu1011Asp (c.3033G>C) is low-frequency (popmax 1.13%, afr) (gnomAD).

What do computational predictors say about C5 p.Glu1011Asp (c.3033G>C)?

AlphaMissense predicts likely pathogenic (score 0.5832) — an in-silico prediction, not a clinical call.

C5 p.Glu1011Asp

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

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

c.3033G>C · rs150096192 · VCV717915

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.5832 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement component 5 deficiency

Computational evidence

Protein change
AlphaMissense	0.5832	likely pathogenic
REVEL	0.197	benign-leaning
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -4
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	18.79	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 1.13% African / African-American · 847/75,024 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.0679% 1,096/1,614,002 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.13%	89
Middle Eastern	0.297%	337
Remaining individualsnot grpmax-eligible	0.118%	845
Admixed American	0.0983%	1,017
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,400
European (non-Finnish)	0.00771%	12,966
South Asian	0.00329%	30,355

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: C5
Protein: p.Glu1011Asp
Coding: c.3033G>C
MANE Select: NM_001735
dbSNP: rs150096192
Type: single nucleotide variant
Location: chr9:120989689 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 1011: an α-helix; a disulfide bond; a UniProt-annotated variant site (in c5d)

Full C5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component 5 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C5 c.2257+1G>A Likely pathogenic ★★ same condition
C5 c.4679-2A>G Likely pathogenic ★★ same condition
C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same condition
C5 p.Gln19Ter Pathogenic ★★ same condition
C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same condition
C5 c.2059+3A>G Uncertain significance ★★ same condition
C5 c.4081-6A>G Uncertain significance ★★ same condition
C5 c.4504+4A>G 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/c5-p-glu1011asp (accessed [today's date]).

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