Is ASTE1 p.Pro465Arg (c.1394C>G) pathogenic?

ASTE1 p.Pro465Arg (c.1394C>G) is classified Uncertain significance in ASTE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.6823); Absent from gnomAD v4.1.

How common is ASTE1 p.Pro465Arg (c.1394C>G) in the general population?

ASTE1 p.Pro465Arg (c.1394C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASTE1 p.Pro465Arg (c.1394C>G)?

AlphaMissense predicts likely pathogenic (score 0.6823) — an in-silico prediction, not a clinical call.

ASTE1 p.Pro465Arg

c.1394C>G · VCV4643569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6823 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6823	likely pathogenic
REVEL	0.411	indeterminate
SaProt	LLR -11.72	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0008 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ASTE1
Protein: p.Pro465Arg
Coding: c.1394C>G
MANE Select: NM_014065
Type: single nucleotide variant
Location: chr3:131018625 (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-pro465arg (accessed [today's date]).

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