Is C1QB p.Pro45Arg (c.134C>G) pathogenic?

C1QB p.Pro45Arg (c.134C>G) is classified Uncertain significance in C1QB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely benign (0.1053); Very rare (popmax 8.48e-05%, nfe); Associated with C1Q deficiency 2.

What condition is associated with C1QB p.Pro45Arg (c.134C>G)?

C1QB p.Pro45Arg (c.134C>G) is associated with C1Q deficiency 2 (ClinVar).

How common is C1QB p.Pro45Arg (c.134C>G) in the general population?

C1QB p.Pro45Arg (c.134C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about C1QB p.Pro45Arg (c.134C>G)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

C1QB p.Pro45Arg

c.134C>G · VCV3580831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

C1Q deficiency 2

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,920 bp · p 0.012 · regional, not allelic
Overall
CADD	22.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P47R vs ClinVar P45R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,922 alleles

Overall 6.84e-05% 1/1,461,686 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: C1QB
Protein: p.Pro45Arg
Coding: c.134C>G
MANE Select: NM_001378156
Type: single nucleotide variant
Location: chr1:22659596 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI 0.25 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 11 PDB
Residue 45: the collagen-like 1 domain; the 'disordered' region

Full C1QB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C1Q deficiency 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C1QB p.Pro45= Likely benign ★ same residue
C1QB p.Arg175Ter Likely pathogenic ★★ same condition
C1QB p.Arg134Trp Uncertain significance ★★ ⚠ same condition
C1QB p.Arg186Gln Uncertain significance ★★ ⚠ same condition
C1QB p.Asp21Asn Uncertain significance ★★ ⚠ same condition
C1QB p.Asp68Gly Uncertain significance ★★ ⚠ same condition
C1QB p.Gly31Arg Uncertain significance ★★ ⚠ same condition
C1QB p.Pro32His Uncertain significance ★★ ⚠ same condition

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/c1qb-p-pro45arg (accessed [today's date]).

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