Is C3 p.Ser798= (c.2394C>T) pathogenic?

C3 p.Ser798= (c.2394C>T) is classified Benign/Likely benign in C3 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-09-17). Rare (popmax 0.818%, afr); Associated with age related macular degeneration 9.

What condition is associated with C3 p.Ser798= (c.2394C>T)?

C3 p.Ser798= (c.2394C>T) is associated with age related macular degeneration 9, atypical hemolytic-uremic syndrome with C3 anomaly, complement component 3 deficiency (ClinVar).

How common is C3 p.Ser798= (c.2394C>T) in the general population?

C3 p.Ser798= (c.2394C>T) is rare (popmax 0.818%, afr) (gnomAD).

C3 p.Ser798=

c.2394C>T · rs112178657 · VCV330307

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.818%, afr)

Conditions

age related macular degeneration 9

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 4.1	GERP 0.71, phastCons 1
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.818% African / African-American · 612/74,858 alleles

Filtering AF 0.764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.743%

Overall 0.0443% 712/1,606,570 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.818%	122
Middle Eastern	0.0827%	1,209
Remaining individualsnot grpmax-eligible	0.0626%	1,597
Admixed American	0.055%	1,818
South Asian	0.0022%	45,475
European (non-Finnish)	0.00179%	55,942

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: C3
Protein: p.Ser798=
Coding: c.2394C>T
MANE Select: NM_000064
dbSNP: rs112178657
Type: single nucleotide variant
Location: chr19:6702173 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 798: a disulfide bond

Full C3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: atypical hemolytic-uremic syndrome with C3 anomaly complement component 3 deficiency C3 glomerulonephritis atypical hemolytic-uremic syndrome

Similar variants

C3 c.1003+1G>A Pathogenic/Likely pathogenic ★★ same condition
C3 c.2863+1G>T Likely pathogenic ★★ same condition
C3 c.4030-2A>G Likely pathogenic ★★ same condition
C3 p.Arg161Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
C3 p.Arg592Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
C3 p.Arg592Trp Likely pathogenic ★★ ⚠ same condition
C3 p.Arg764Ter Pathogenic/Likely pathogenic ★★ same condition
C3 p.Ile1157Thr Pathogenic/Likely 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/c3-p-ser798 (accessed [today's date]).

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