Is C1QA p.Pro73Ala (c.217C>G) pathogenic?

C1QA p.Pro73Ala (c.217C>G) is classified Uncertain significance in C1QA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.0697); Very rare (popmax 8.53e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with C1QA p.Pro73Ala (c.217C>G)?

C1QA p.Pro73Ala (c.217C>G) is associated with Inborn genetic diseases (ClinVar).

How common is C1QA p.Pro73Ala (c.217C>G) in the general population?

C1QA p.Pro73Ala (c.217C>G) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about C1QA p.Pro73Ala (c.217C>G)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

C1QA p.Pro73Ala

c.217C>G · rs758718727 · VCV2541997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -7.91	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 0.068	GERP -0.65
Regional constraint	o/e 0.84	unconstrained · MANE · 1,787 bp · p 0.003 · regional, not allelic
Overall
CADD	12.67	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 8.53e-05% European (non-Finnish) · 1/1,172,096 alleles

Overall 6.92e-05% 1/1,444,058 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: C1QA
Protein: p.Pro73Ala
Coding: c.217C>G
MANE Select: NM_015991
dbSNP: rs758718727
Type: single nucleotide variant
Location: chr1:22638886 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 11 PDB
Residue 73: 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

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

Similar variants

C1QA p.Pro73Leu Uncertain significance ★ ⚠ same residue
C1QA p.Arg150Gln Uncertain significance ★★ ⚠ same condition
C1QA p.Arg180Lys Uncertain significance ★★ ⚠ same condition
C1QA p.Arg44Gln 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

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-pro73ala (accessed [today's date]).

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