Is C5 p.Ser147= (c.441G>A) pathogenic?

C5 p.Ser147= (c.441G>A) is classified Likely benign in C5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-10). Ultra-rare (popmax 0.0327%, sas); Associated with complement component 5 deficiency.

What condition is associated with C5 p.Ser147= (c.441G>A)?

C5 p.Ser147= (c.441G>A) is associated with complement component 5 deficiency (ClinVar).

How common is C5 p.Ser147= (c.441G>A) in the general population?

C5 p.Ser147= (c.441G>A) is ultra-rare (popmax 0.0327%, sas) (gnomAD).

C5 p.Ser147=

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.441G>A · rs376535022 · VCV1605873

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0327%, sas)

Conditions

complement component 5 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -0.92
Overall
CADD	7.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0327% South Asian · 27/82,588 alleles

Filtering AF 0.023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.0056% 85/1,516,510 alleles · ultra-rare exomes 76/1,364,506 · genomes 9/152,004 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0327%	3,059
European (non-Finnish)	0.00489%	20,452
Remaining individualsnot grpmax-eligible	0.00342%	29,272
African / African-American	0.00276%	36,277

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.Ser147=
Coding: c.441G>A
MANE Select: NM_001735
dbSNP: rs376535022
Type: single nucleotide variant
Location: chr9:121037932 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 147: a UniProt-annotated variant site (in c5d); a β-strand

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-ser147 (accessed [today's date]).

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