Is C1R p.Pro9= (c.27G>A) pathogenic?

C1R p.Pro9= (c.27G>A) is classified Benign/Likely benign in C1R (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-06). Rare (popmax 0.432%, mid).

How common is C1R p.Pro9= (c.27G>A) in the general population?

C1R p.Pro9= (c.27G>A) is rare (popmax 0.432%, mid) (gnomAD).

C1R p.Pro9=

c.27G>A · rs146478898 · VCV1175815

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.432%, mid)

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 -20	GERP -2.7
Overall
CADD	0.121	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.432% Middle Eastern · 19/4,398 alleles

Filtering AF 0.414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.408%

Overall 0.33% 2,467/747,114 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.03%	97
Middle Easterngrpmax	0.432%	231
European (non-Finnish)	0.431%	232
Remaining individualsnot grpmax-eligible	0.409%	245
Admixed American	0.384%	261
Finnishnot grpmax-eligible	0.107%	933
African / African-American	0.089%	1,123
South Asian	0.0128%	7,798
East Asian	0.00506%	19,764

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: C1R
Protein: p.Pro9=
Coding: c.27G>A
MANE Select: NM_001733
dbSNP: rs146478898
Type: single nucleotide variant
Location: chr12:7091656 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 87.33 · 12 PDB

Full C1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1R p.Pro9Leu Likely benign ★★ same residue
C1R p.Arg301Pro Pathogenic ★★ ⚠ same type
C1R p.Asp290Gly Pathogenic/Likely pathogenic ★★ same type
C1R p.Cys338Arg Pathogenic ★★ same type
C1R p.Cys371Trp Pathogenic ★★ same type
C1R p.Gly297Asp Pathogenic/Likely pathogenic ★★ same type
C1R p.His642Gln Uncertain significance ★★ ⚠ same type
C1R p.Leu285Met 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/c1r-p-pro9 (accessed [today's date]).

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