Is STAC3 p.Pro89Ser (c.265C>T) pathogenic?

STAC3 p.Pro89Ser (c.265C>T) is classified Uncertain significance in STAC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: ambiguous (0.455); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with STAC3 p.Pro89Ser (c.265C>T)?

STAC3 p.Pro89Ser (c.265C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STAC3 p.Pro89Ser (c.265C>T) in the general population?

STAC3 p.Pro89Ser (c.265C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAC3 p.Pro89Ser (c.265C>T)?

AlphaMissense predicts ambiguous (score 0.455) — an in-silico prediction, not a clinical call.

STAC3 p.Pro89Ser

c.265C>T · VCV3802100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.455	ambiguous
REVEL	0.482	indeterminate
SaProt	LLR -11.53	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 0.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,821 bp · p 0.043 · regional, not allelic
Overall
CADD	28.6	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: STAC3
Protein: p.Pro89Ser
Coding: c.265C>T
MANE Select: NM_145064
Type: single nucleotide variant
Location: chr12:57249110 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06 · 5 PDB
Residue 89: a β-strand; the 'disordered' region

Full STAC3 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

STAC3 p.Ala341Val Uncertain significance ★★ ⚠ same condition
STAC3 p.Arg321His Uncertain significance ★★ ⚠ same condition
STAC3 p.Glu210Asp Uncertain significance ★★ ⚠ same condition
STAC3 p.Glu212Asp Uncertain significance ★★ ⚠ same condition
STAC3 p.Glu51Gln Uncertain significance ★★ ⚠ same condition
STAC3 p.Gly142Arg Uncertain significance ★★ ⚠ same condition
STAC3 p.Gly57Asp Uncertain significance ★★ ⚠ same condition
STAC3 p.Ile364Phe 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/stac3-p-pro89ser (accessed [today's date]).

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