Is C5AR2 p.Arg204Pro (c.611G>C) pathogenic?

C5AR2 p.Arg204Pro (c.611G>C) is classified Uncertain significance in C5AR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: likely pathogenic (0.7699); Very rare (popmax 0.00267%, afr).

How common is C5AR2 p.Arg204Pro (c.611G>C) in the general population?

C5AR2 p.Arg204Pro (c.611G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about C5AR2 p.Arg204Pro (c.611G>C)?

AlphaMissense predicts likely pathogenic (score 0.7699) — an in-silico prediction, not a clinical call.

C5AR2 p.Arg204Pro

c.611G>C · rs140624718 · VCV2268679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7699 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7699	likely pathogenic · top 8% in C5AR2
REVEL	0.551	indeterminate
SaProt	LLR -13.06	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,010 bp · p 0.66 · regional, not allelic
Overall
CADD	22.7	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

Grpmax group 0.00267% African / African-American · 2/74,898 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,612,464 alleles · very rare exomes 1/1,460,358 · genomes 1/152,106 · joint denominator

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: C5AR2
Protein: p.Arg204Pro
Coding: c.611G>C
MANE Select: NM_001271749
dbSNP: rs140624718
Type: single nucleotide variant
Location: chr19:47341410 (GRCh38)
Gene constraint: LOEUF 1.788 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 86.24 · 7 PDB

Full C5AR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C5AR2 p.Arg204Gln Uncertain significance ★ same residue
C5AR2 p.Arg204= Likely benign ★ same residue
C5AR2 p.Ile171Thr Uncertain significance ★★ ⚠ same type
C5AR2 p.His329Arg Benign ★★ same type
C5AR2 p.Leu281= Benign ★★ same type
C5AR2 p.Leu299Val Benign/Likely benign ★★ same type
C5AR2 p.Ser17= Benign ★★ same type
C5AR2 p.Ala136Thr 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/c5ar2-p-arg204pro (accessed [today's date]).

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