Is C3 p.Asp797Val (c.2390A>T) pathogenic?

C3 p.Asp797Val (c.2390A>T) is classified Uncertain significance in C3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-30). AlphaMissense: likely pathogenic (0.9103); Absent from gnomAD v4.1; Associated with C3 glomerulonephritis.

What condition is associated with C3 p.Asp797Val (c.2390A>T)?

C3 p.Asp797Val (c.2390A>T) is associated with C3 glomerulonephritis (ClinVar).

How common is C3 p.Asp797Val (c.2390A>T) in the general population?

C3 p.Asp797Val (c.2390A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C3 p.Asp797Val (c.2390A>T)?

AlphaMissense predicts likely pathogenic (score 0.9103) — an in-silico prediction, not a clinical call.

C3 p.Asp797Val

c.2390A>T · rs1967690681 · VCV1721768

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9103 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C3 glomerulonephritis

Computational evidence

Protein change
AlphaMissense	0.9103	likely pathogenic
REVEL	0.649	pathogenic-leaning
SaProt	LLR -17.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 35 kb · p 3.5e-28 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C3
Protein: p.Asp797Val
Coding: c.2390A>T
MANE Select: NM_000064
dbSNP: rs1967690681
Type: single nucleotide variant
Location: chr19:6702177 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 797: a disulfide bond

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

Disease context

C3 glomerulonephritis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C3 p.Asp797Ala Uncertain significance ★ ⚠ same residue
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.Ala257Thr Uncertain significance ★★ ⚠ same condition
C3 p.Arg1042Gln Uncertain significance ★★ ⚠ same condition
C3 p.Arg1072Trp Uncertain significance ★★ ⚠ same condition
C3 p.Arg1219Cys 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-asp797val (accessed [today's date]).

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