Is C1QB p.Pro9Ser (c.25C>T) pathogenic?

C1QB p.Pro9Ser (c.25C>T) is classified Uncertain significance in C1QB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-27). AlphaMissense: likely benign (0.0716); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with C1QB p.Pro9Ser (c.25C>T)?

C1QB p.Pro9Ser (c.25C>T) is associated with Inborn genetic diseases (ClinVar).

How common is C1QB p.Pro9Ser (c.25C>T) in the general population?

C1QB p.Pro9Ser (c.25C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about C1QB p.Pro9Ser (c.25C>T)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

C1QB p.Pro9Ser

c.25C>T · rs779270876 · VCV1493957

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -2.7
Regional constraint	o/e 0.86	unconstrained · MANE · 1,920 bp · p 0.012 · regional, not allelic
Overall
CADD	0.319	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 P11S vs ClinVar P9S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,834 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00477% 77/1,613,870 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.189%	529
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-Americangrpmax	0.00134%	74,834
European (non-Finnish)	0.000847%	117,997

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: C1QB
Protein: p.Pro9Ser
Coding: c.25C>T
MANE Select: NM_001378156
dbSNP: rs779270876
Type: single nucleotide variant
Location: chr1:22659487 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI 0.25 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 11 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C1QB p.Pro9Leu Uncertain significance ★ ⚠ same residue
C1QB p.Arg134Gln Uncertain significance ★★ ⚠ 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.Asp226Glu Uncertain significance ★★ ⚠ same condition
C1QB p.Asp48Asn Uncertain significance ★★ ⚠ same condition
C1QB p.Asp68Gly 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-pro9ser (accessed [today's date]).

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