Is C1QA p.Arg44Gln (c.131G>A) pathogenic?

C1QA p.Arg44Gln (c.131G>A) is classified Uncertain significance in C1QA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-28). AlphaMissense: likely benign (0.0985); Very rare (popmax 0.00559%, sas); Associated with Inborn genetic diseases.

What condition is associated with C1QA p.Arg44Gln (c.131G>A)?

C1QA p.Arg44Gln (c.131G>A) is associated with Inborn genetic diseases (ClinVar).

How common is C1QA p.Arg44Gln (c.131G>A) in the general population?

C1QA p.Arg44Gln (c.131G>A) is very rare (popmax 0.00559%, sas) (gnomAD).

What do computational predictors say about C1QA p.Arg44Gln (c.131G>A)?

AlphaMissense predicts likely benign (score 0.0985) — an in-silico prediction, not a clinical call.

C1QA p.Arg44Gln

c.131G>A · rs757112554 · VCV1410703

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00559%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0985	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -7.61	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 3.9	GERP 0.46, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,787 bp · p 0.003 · 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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00559% South Asian · 5/89,488 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.000873% 14/1,603,668 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00559%	17,898
Remaining individualsnot grpmax-eligible	0.00484%	20,675
Admixed American	0.00345%	28,979
East Asian	0.00224%	44,586
European (non-Finnish)	0.000255%	391,940

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.Arg44Gln
Coding: c.131G>A
MANE Select: NM_015991
dbSNP: rs757112554
Type: single nucleotide variant
Location: chr1:22637747 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 11 PDB
Residue 44: the collagen-like domain; the 'disordered' region

Full C1QA 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

C1QA p.Arg44Trp Uncertain significance ★ ⚠ same residue
C1QA p.Arg150Gln Uncertain significance ★★ ⚠ same condition
C1QA p.Arg180Lys Uncertain significance ★★ ⚠ same condition
C1QA p.Arg60Gln Uncertain significance ★★ ⚠ same condition
C1QA p.Arg60Trp Uncertain significance ★★ ⚠ same condition
C1QA p.Asp213Glu Uncertain significance ★★ same condition
C1QA p.Met126Ile Uncertain significance ★★ ⚠ same condition
C1QA p.Phe242Leu 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/c1qa-p-arg44gln (accessed [today's date]).

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