Is STAG3 p.Pro1104Ser (c.3310C>T) pathogenic?

STAG3 p.Pro1104Ser (c.3310C>T) is classified Uncertain significance in STAG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). AlphaMissense: likely benign (0.075); Ultra-rare (popmax 0.0227%, afr); Associated with Inborn genetic diseases.

What condition is associated with STAG3 p.Pro1104Ser (c.3310C>T)?

STAG3 p.Pro1104Ser (c.3310C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STAG3 p.Pro1104Ser (c.3310C>T) in the general population?

STAG3 p.Pro1104Ser (c.3310C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about STAG3 p.Pro1104Ser (c.3310C>T)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

STAG3 p.Pro1104Ser

c.3310C>T · rs781521756 · VCV2552544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.60	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 0.69	GERP -1.3, phastCons 0.001
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.0088 · regional, not allelic
Overall
CADD	6.647	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 0.0227% African / African-American · 17/74,976 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00118% 19/1,613,568 alleles · ultra-rare exomes 10/1,461,396 · genomes 9/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,410
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asian	0.0011%	91,038

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: STAG3
Protein: p.Pro1104Ser
Coding: c.3310C>T
MANE Select: NM_001282717
dbSNP: rs781521756
Type: single nucleotide variant
Location: chr7:100211082 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.46
Residue 1104: a UniProt-annotated variant site (in spgf61); a UniProt-annotated variant site (in pof8); the 'disordered' region

Full STAG3 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

STAG3 p.Cys784Ser Uncertain significance ★★ same condition
STAG3 p.Pro4Leu Uncertain significance ★★ ⚠ same condition
STAG3 p.Ala1082Gly Uncertain significance ★ ⚠ same condition
STAG3 p.Ala1143Thr Uncertain significance ★ ⚠ same condition
STAG3 p.Ala250Val Uncertain significance ★ ⚠ same condition
STAG3 p.Ala424Val Uncertain significance ★ ⚠ same condition
STAG3 p.Ala444Thr Uncertain significance ★ ⚠ same condition
STAG3 p.Ala473Thr 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/stag3-p-pro1104ser (accessed [today's date]).

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