Is ASTL p.Ser429Pro (c.1285T>C) pathogenic?

ASTL p.Ser429Pro (c.1285T>C) is classified Likely benign in ASTL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0539); Absent from gnomAD v4.1.

How common is ASTL p.Ser429Pro (c.1285T>C) in the general population?

ASTL p.Ser429Pro (c.1285T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASTL p.Ser429Pro (c.1285T>C)?

AlphaMissense predicts likely benign (score 0.0539) — an in-silico prediction, not a clinical call.

ASTL p.Ser429Pro

c.1285T>C · VCV4157124

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0539 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0539	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -5.79	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 0.97	GERP -2.2, phastCons 0.004
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.041 · regional, not allelic
Overall
CADD	1.234	PHRED · no single calibrated threshold — expert panels disagree

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: ASTL
Protein: p.Ser429Pro
Coding: c.1285T>C
MANE Select: NM_001002036
Type: single nucleotide variant
Location: chr2:96123861 (GRCh38)
Gene constraint: LOEUF 1.024 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.90 · 1 PDB
Residue 429: the 'disordered' region

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

Similar variants

ASTL p.Ala125Glu Uncertain significance ★ ⚠ same type
ASTL p.Ala125Val Uncertain significance ★ ⚠ same type
ASTL p.Ala24Pro Uncertain significance ★ ⚠ same type
ASTL p.Ala24Val Uncertain significance ★ ⚠ same type
ASTL p.Ala318Val Uncertain significance ★ ⚠ same type
ASTL p.Ala31Thr Uncertain significance ★ ⚠ same type
ASTL p.Ala330Val Uncertain significance ★ ⚠ same type
ASTL p.Ala367Pro 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/astl-p-ser429pro (accessed [today's date]).

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