Is C5AR2 p.Phe291Cys (c.872T>G) pathogenic?

C5AR2 p.Phe291Cys (c.872T>G) is classified Uncertain significance in C5AR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.6552); Absent from gnomAD v4.1.

How common is C5AR2 p.Phe291Cys (c.872T>G) in the general population?

C5AR2 p.Phe291Cys (c.872T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C5AR2 p.Phe291Cys (c.872T>G)?

AlphaMissense predicts likely pathogenic (score 0.6552) — an in-silico prediction, not a clinical call.

C5AR2 p.Phe291Cys

c.872T>G · rs2514906872 · VCV2283980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6552 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6552	likely pathogenic
REVEL	0.342	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.86, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,010 bp · p 0.66 · regional, not allelic
Overall
CADD	24.7	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

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: C5AR2
Protein: p.Phe291Cys
Coding: c.872T>G
MANE Select: NM_001271749
dbSNP: rs2514906872
Type: single nucleotide variant
Location: chr19:47341671 (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.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
C5AR2 p.Ala170Thr Uncertain significance ★ ⚠ same type
C5AR2 p.Ala199Thr 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-phe291cys (accessed [today's date]).

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