Is C5AR2 p.Pro38= (c.114G>A) pathogenic?

C5AR2 p.Pro38= (c.114G>A) is classified Likely benign in C5AR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). Ultra-rare (popmax 0.0136%, nfe).

How common is C5AR2 p.Pro38= (c.114G>A) in the general population?

C5AR2 p.Pro38= (c.114G>A) is ultra-rare (popmax 0.0136%, nfe) (gnomAD).

C5AR2 p.Pro38=

c.114G>A · VCV3994128

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.4	GERP -3.6
Overall
CADD	0.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% European (non-Finnish) · 161/1,179,948 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.0104% 167/1,612,534 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0136%	7,329
African / African-American	0.00667%	14,989
South Asian	0.0011%	91,084

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.Pro38=
Coding: c.114G>A
MANE Select: NM_001271749
Type: single nucleotide variant
Location: chr19:47340913 (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.Pro38Leu Uncertain significance ★ ⚠ 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
C5AR2 p.Ala170Thr 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-pro38 (accessed [today's date]).

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