Is ASPRV1 p.Ala2Pro (c.4G>C) pathogenic?

ASPRV1 p.Ala2Pro (c.4G>C) is classified Uncertain significance in ASPRV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.2546); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with ASPRV1 p.Ala2Pro (c.4G>C)?

ASPRV1 p.Ala2Pro (c.4G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASPRV1 p.Ala2Pro (c.4G>C) in the general population?

ASPRV1 p.Ala2Pro (c.4G>C) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ASPRV1 p.Ala2Pro (c.4G>C)?

AlphaMissense predicts likely benign (score 0.2546) — an in-silico prediction, not a clinical call.

ASPRV1 p.Ala2Pro

c.4G>C · rs775218716 · VCV2492991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2546	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -7.33	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 3.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.7	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 A86P vs ClinVar A2P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,086 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,613,968 alleles · very rare exomes 3/1,461,764 · genomes 1/152,204 · joint denominator

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.Ala2Pro
Coding: c.4G>C
MANE Select: NM_152792
dbSNP: rs775218716
Type: single nucleotide variant
Location: chr2:69961433 (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 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
ASPRV1 c.-158C>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-ala2pro (accessed [today's date]).

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