Is ASPRV1 p.Val28Ile (c.82G>A) pathogenic?

ASPRV1 p.Val28Ile (c.82G>A) is classified Uncertain significance in ASPRV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely benign (0.0902); Very rare (popmax 0.00533%, afr); Associated with Inborn genetic diseases.

What condition is associated with ASPRV1 p.Val28Ile (c.82G>A)?

ASPRV1 p.Val28Ile (c.82G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASPRV1 p.Val28Ile (c.82G>A) in the general population?

ASPRV1 p.Val28Ile (c.82G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about ASPRV1 p.Val28Ile (c.82G>A)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

ASPRV1 p.Val28Ile

c.82G>A · VCV3318753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.62	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 0.29	GERP -1.9
Regional constraint	o/e 0.93	unconstrained · MANE · 776 bp · p 0.24 · regional, not allelic
Overall
CADD	6.186	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 V112I vs ClinVar V28I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,012 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00167% 27/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,753
Finnishnot grpmax-eligible	0.00469%	21,325
South Asian	0.00439%	22,769
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.00119%	84,288

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.Val28Ile
Coding: c.82G>A
MANE Select: NM_152792
Type: single nucleotide variant
Location: chr2:69961355 (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-val28ile (accessed [today's date]).

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