Is ASTE1 p.Ile596Val (c.1786A>G) pathogenic?

ASTE1 p.Ile596Val (c.1786A>G) is classified Uncertain significance in ASTE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.0607); Very rare (popmax 0.00446%, eas).

How common is ASTE1 p.Ile596Val (c.1786A>G) in the general population?

ASTE1 p.Ile596Val (c.1786A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ASTE1 p.Ile596Val (c.1786A>G)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

ASTE1 p.Ile596Val

c.1786A>G · VCV3954292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -4.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6.9	GERP -5.4
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0008 · regional, not allelic
Overall
CADD	0.094	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 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000205% 3/1,461,730 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
South Asian	0.0011%	91,032

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: ASTE1
Protein: p.Ile596Val
Coding: c.1786A>G
MANE Select: NM_001378687 · reported on NM_014065
Type: single nucleotide variant
Location: chr3:131014311 (GRCh38)

Full ASTE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/aste1-p-ile596val (accessed [today's date]).

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