Is STAG2 p.Ser1007Phe (c.3020C>T) pathogenic?

STAG2 p.Ser1007Phe (c.3020C>T) is classified Uncertain significance in STAG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with STAG2 p.Ser1007Phe (c.3020C>T)?

STAG2 p.Ser1007Phe (c.3020C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STAG2 p.Ser1007Phe (c.3020C>T) in the general population?

STAG2 p.Ser1007Phe (c.3020C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAG2 p.Ser1007Phe (c.3020C>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

STAG2 p.Ser1007Phe

c.3020C>T · rs2059015903 · VCV2127245

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 6% in STAG2
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -14.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 49 kb · p 1.5e-34 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: STAG2
Protein: p.Ser1007Phe
Coding: c.3020C>T
MANE Select: NM_001042750
dbSNP: rs2059015903
Type: single nucleotide variant
Location: chrX:124083516 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 1007: an α-helix; a UniProt-annotated variant site (in hpe13 and mkms; patient cells show decreased protein abundance; increased sister chromatid cohesion); a UniProt-annotated variant site (in mkms); a UniProt-annotated variant site (in hpe13)

Full STAG2 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

STAG2 p.Ala787Gly Uncertain significance ★★ same condition
STAG2 p.Arg146Gln Uncertain significance ★★ ⚠ same condition
STAG2 p.Asn618Ser Uncertain significance ★★ ⚠ same condition
STAG2 p.Asp651Glu Uncertain significance ★★ ⚠ same condition
STAG2 p.Asp850Asn Uncertain significance ★★ ⚠ same condition
STAG2 p.Gln1173Glu Uncertain significance ★★ same condition
STAG2 p.Gly935Cys Uncertain significance ★★ ⚠ same condition
STAG2 p.Pro1113Ser 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/stag2-p-ser1007phe (accessed [today's date]).

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