Is STAC3 p.Pro43Ser (c.127C>T) pathogenic?

STAC3 p.Pro43Ser (c.127C>T) is classified Uncertain significance in STAC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). AlphaMissense: likely benign (0.0755); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with STAC3 p.Pro43Ser (c.127C>T)?

STAC3 p.Pro43Ser (c.127C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STAC3 p.Pro43Ser (c.127C>T) in the general population?

STAC3 p.Pro43Ser (c.127C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about STAC3 p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

STAC3 p.Pro43Ser

c.127C>T · rs1235731703 · VCV3170864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -6.66	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 3	GERP -1.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,821 bp · p 0.043 · regional, not allelic
Overall
CADD	16.53	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 0.00668% East Asian · 3/44,880 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,613,846 alleles · very rare exomes 3/1,461,596 · genomes 0/152,250 · joint denominator

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: STAC3
Protein: p.Pro43Ser
Coding: c.127C>T
MANE Select: NM_145064
dbSNP: rs1235731703
Type: single nucleotide variant
Location: chr12:57249248 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06 · 5 PDB
Residue 43: 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.Pro43= Likely benign ★ same residue
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

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-pro43ser (accessed [today's date]).

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