Is ASTE1 p.Val77Ile (c.229G>A) pathogenic?

ASTE1 p.Val77Ile (c.229G>A) is classified Uncertain significance in ASTE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.0807); Very rare (popmax 0.0011%, sas).

How common is ASTE1 p.Val77Ile (c.229G>A) in the general population?

ASTE1 p.Val77Ile (c.229G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ASTE1 p.Val77Ile (c.229G>A)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

ASTE1 p.Val77Ile

c.229G>A · VCV3954364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -9.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -2.4, phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0008 · regional, not allelic
Overall
CADD	17.42	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 0.0011% South Asian · 1/90,888 alleles

Overall 6.85e-05% 1/1,460,474 alleles · very rare

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.Val77Ile
Coding: c.229G>A
MANE Select: NM_014065
Type: single nucleotide variant
Location: chr3:131025078 (GRCh38)
Gene constraint: LOEUF 1.291 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40

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

Similar variants

ASTE1 p.Ala202Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala219Val Uncertain significance ★ ⚠ same type
ASTE1 p.Ala239Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala514Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala69Pro Uncertain significance ★ ⚠ same type
ASTE1 p.Arg143Trp Uncertain significance ★ ⚠ same type
ASTE1 p.Arg240His Uncertain significance ★ ⚠ same type
ASTE1 p.Arg255Gln Uncertain significance ★ ⚠ same type

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-val77ile (accessed [today's date]).

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