Is C3 p.Ala806Ser (c.2416G>T) pathogenic?

C3 p.Ala806Ser (c.2416G>T) is classified Uncertain significance in C3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-13). AlphaMissense: ambiguous (0.3571); Very rare (popmax 0.00134%, afr); Associated with age related macular degeneration 9.

What condition is associated with C3 p.Ala806Ser (c.2416G>T)?

C3 p.Ala806Ser (c.2416G>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.Ala806Ser (c.2416G>T) in the general population?

C3 p.Ala806Ser (c.2416G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about C3 p.Ala806Ser (c.2416G>T)?

AlphaMissense predicts ambiguous (score 0.3571) — an in-silico prediction, not a clinical call.

C3 p.Ala806Ser

c.2416G>T · rs1448441857 · VCV2798308

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3571 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

age related macular degeneration 9

Computational evidence

Protein change
AlphaMissense	0.3571	ambiguous
REVEL	0.389	indeterminate
SaProt	LLR -9.16	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 35 kb · p 3.5e-28 · regional, not allelic
Overall
CADD	24.5	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 0.00134% African / African-American · 1/74,780 alleles

Overall 6.89e-05% 1/1,452,220 alleles · very rare

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.Ala806Ser
Coding: c.2416G>T
MANE Select: NM_000064
dbSNP: rs1448441857
Type: single nucleotide variant
Location: chr19:6702151 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 806: a β-strand; 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

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 c.683-3C>A 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/c3-p-ala806ser (accessed [today's date]).

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