Is ASPRV1 p.Pro19Gln (c.56C>A) pathogenic?

ASPRV1 p.Pro19Gln (c.56C>A) is classified Uncertain significance in ASPRV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely pathogenic (0.693); Very rare (popmax 0.00237%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ASPRV1 p.Pro19Gln (c.56C>A)?

ASPRV1 p.Pro19Gln (c.56C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASPRV1 p.Pro19Gln (c.56C>A) in the general population?

ASPRV1 p.Pro19Gln (c.56C>A) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about ASPRV1 p.Pro19Gln (c.56C>A)?

AlphaMissense predicts likely pathogenic (score 0.693) — an in-silico prediction, not a clinical call.

ASPRV1 p.Pro19Gln

c.56C>A · VCV4156524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.693	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -12.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.14, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 776 bp · p 0.24 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 P103Q vs ClinVar P19Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,180,034 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0018% 29/1,613,982 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,144
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: ASPRV1
Protein: p.Pro19Gln
Coding: c.56C>A
MANE Select: NM_152792
Type: single nucleotide variant
Location: chr2:69961381 (GRCh38)
Gene constraint: LOEUF 1.252 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 7 PDB

Full ASPRV1 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

ASPRV1 p.Pro19Leu Uncertain significance ★ ⚠ same residue
ASPRV1 c.17C>A Uncertain significance ★ ⚠ same condition
ASPRV1 c.17C>T Uncertain significance ★ same condition
ASPRV1 c.20G>A Uncertain significance ★ ⚠ same condition
ASPRV1 c.23T>C Uncertain significance ★ ⚠ same condition
ASPRV1 c.-125C>T Uncertain significance ★ ⚠ same condition
ASPRV1 c.-126G>A Uncertain significance ★ ⚠ same condition
ASPRV1 c.-152C>T 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/asprv1-p-pro19gln (accessed [today's date]).

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