Is STAC3 p.Pro77Ser (c.229C>T) pathogenic?

STAC3 p.Pro77Ser (c.229C>T) is classified Uncertain significance in STAC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.1359); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with STAC3 p.Pro77Ser (c.229C>T)?

STAC3 p.Pro77Ser (c.229C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STAC3 p.Pro77Ser (c.229C>T) in the general population?

STAC3 p.Pro77Ser (c.229C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAC3 p.Pro77Ser (c.229C>T)?

AlphaMissense predicts likely benign (score 0.1359) — an in-silico prediction, not a clinical call.

STAC3 p.Pro77Ser

c.229C>T · VCV3962883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1359 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1359	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -3.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,821 bp · p 0.043 · regional, not allelic
Overall
CADD	18.2	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

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.Pro77Ser
Coding: c.229C>T
MANE Select: NM_145064
Type: single nucleotide variant
Location: chr12:57249146 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06 · 5 PDB
Residue 77: 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-pro77ser (accessed [today's date]).

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