Is C3AR1 p.Ser373Arg (c.1119C>G) pathogenic?

C3AR1 p.Ser373Arg (c.1119C>G) is classified Uncertain significance in C3AR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.1704); Very rare (popmax 0.00169%, nfe).

How common is C3AR1 p.Ser373Arg (c.1119C>G) in the general population?

C3AR1 p.Ser373Arg (c.1119C>G) is very rare (popmax 0.00169%, nfe) (gnomAD).

What do computational predictors say about C3AR1 p.Ser373Arg (c.1119C>G)?

AlphaMissense predicts likely benign (score 0.1704) — an in-silico prediction, not a clinical call.

C3AR1 p.Ser373Arg

c.1119C>G · rs777724881 · VCV3135990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1704	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -5.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -1.3, phastCons 0.28
Regional constraint	o/e 0.99	unconstrained · MANE · 1,445 bp · p 0.85 · regional, not allelic
Overall
CADD	11.68	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,036 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00137% 20/1,461,872 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: C3AR1
Protein: p.Ser373Arg
Coding: c.1119C>G
MANE Select: NM_004054
dbSNP: rs777724881
Type: single nucleotide variant
Location: chr12:8059067 (GRCh38)
Gene constraint: LOEUF 1.58 · pLI 0.32 (gnomAD)
Structure: AlphaFold pLDDT 68.68 · 19 PDB
Residue 373: a β-strand

Full C3AR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C3AR1 p.Pro76Ala Uncertain significance ★★ ⚠ same type
C3AR1 p.Tyr90= Likely benign ★★ same type
C3AR1 p.Val136Ala Benign/Likely benign ★★ same type
C3AR1 p.Val47Gly Benign ★★ same type
C3AR1 c.-8G>A Uncertain significance ★ same type
C3AR1 p.Ala150Asp Uncertain significance ★ ⚠ same type
C3AR1 p.Ala288Asp Uncertain significance ★ ⚠ same type
C3AR1 p.Ala2Val Uncertain significance ★ ⚠ same type

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/c3ar1-p-ser373arg (accessed [today's date]).

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