Is C3 p.Asp588Tyr (c.1762G>T) pathogenic?

C3 p.Asp588Tyr (c.1762G>T) is classified Uncertain significance in C3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-30). AlphaMissense: likely benign (0.3026); Very rare (popmax 0.00133%, afr); Associated with C3 glomerulonephritis.

What condition is associated with C3 p.Asp588Tyr (c.1762G>T)?

C3 p.Asp588Tyr (c.1762G>T) is associated with C3 glomerulonephritis (ClinVar).

How common is C3 p.Asp588Tyr (c.1762G>T) in the general population?

C3 p.Asp588Tyr (c.1762G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about C3 p.Asp588Tyr (c.1762G>T)?

AlphaMissense predicts likely benign (score 0.3026) — an in-silico prediction, not a clinical call.

C3 p.Asp588Tyr

c.1762G>T · VCV3689981

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C3 glomerulonephritis

Computational evidence

Protein change
AlphaMissense	0.3026	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -14.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.013	GERP -3.5, phastCons 0.001
Regional constraint	o/e 0.74	unconstrained · MANE · 35 kb · p 3.5e-28 · regional, not allelic
Overall
CADD	15.32	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 0.00133% African / African-American · 1/75,034 alleles

Overall 6.84e-05% 1/1,461,806 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.Asp588Tyr
Coding: c.1762G>T
MANE Select: NM_000064
Type: single nucleotide variant
Location: chr19:6709767 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 588: a β-strand; 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.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
C3 p.Arg1219His 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-asp588tyr (accessed [today's date]).

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