Is C1QA p.Pro54= (c.162G>A) pathogenic?

C1QA p.Pro54= (c.162G>A) is classified Uncertain significance in C1QA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-12). Ultra-rare (popmax 0.0402%, afr); Associated with C1Q deficiency.

What condition is associated with C1QA p.Pro54= (c.162G>A)?

C1QA p.Pro54= (c.162G>A) is associated with C1Q deficiency (ClinVar).

How common is C1QA p.Pro54= (c.162G>A) in the general population?

C1QA p.Pro54= (c.162G>A) is ultra-rare (popmax 0.0402%, afr) (gnomAD).

C1QA p.Pro54=

Q: How is Immunodeficiency due to a classical component pathway complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.162G>A · rs375714569 · VCV1444785

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0402%, afr)

Conditions

C1Q deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.066	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.1
Overall
CADD	0.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0402% African / African-American · 30/74,538 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0251%

Overall 0.00228% 36/1,575,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0402%	2,485
Middle Eastern	0.0212%	4,714
South Asian	0.00231%	43,281
Admixed American	0.00188%	53,192
Remaining individualsnot grpmax-eligible	0.00164%	61,056
European (non-Finnish)	8.61e-05%	1,160,952

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: C1QA
Protein: p.Pro54=
Coding: c.162G>A
MANE Select: NM_015991
dbSNP: rs375714569
Type: single nucleotide variant
Location: chr1:22637778 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 11 PDB
Residue 54: a modified residue (4-hydroxyproline); the collagen-like domain; the 'disordered' region

Full C1QA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Immunodeficiency due to a classical component pathway complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C1QA p.Pro54Leu Uncertain significance ★ ⚠ same residue
C1QA p.Arg27Ter Pathogenic/Likely pathogenic ★★ same condition
C1QA p.Gln208Ter Pathogenic ★★ same condition
C1QA p.Gly157Asp Likely pathogenic ★★ same condition
C1QA p.Pro4Arg Uncertain significance ★★ ⚠ same condition
C1QA p.Glu23Lys Benign/Likely benign ★★ same condition
C1QA p.Gly92= Benign/Likely benign ★★ same condition
C1QA p.Trp216Ter Pathogenic 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/c1qa-p-pro54 (accessed [today's date]).

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