Is ASPRV1 p.Val18Leu (c.52G>C) pathogenic?

ASPRV1 p.Val18Leu (c.52G>C) is classified Uncertain significance in ASPRV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1079); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASPRV1 p.Val18Leu (c.52G>C)?

ASPRV1 p.Val18Leu (c.52G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASPRV1 p.Val18Leu (c.52G>C) in the general population?

ASPRV1 p.Val18Leu (c.52G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPRV1 p.Val18Leu (c.52G>C)?

AlphaMissense predicts likely benign (score 0.1079) — an in-silico prediction, not a clinical call.

ASPRV1 p.Val18Leu

c.52G>C · VCV4587084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1079 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1079	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -4.70	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 -3.8	GERP -4.5
Regional constraint	o/e 0.93	unconstrained · MANE · 776 bp · p 0.24 · regional, not allelic
Overall
CADD	0.011	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 V102L vs ClinVar V18L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASPRV1
Protein: p.Val18Leu
Coding: c.52G>C
MANE Select: NM_152792
Type: single nucleotide variant
Location: chr2:69961385 (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.Val18Ile Likely benign ★ 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-val18leu (accessed [today's date]).

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