Is STAG2 p.Arg604Pro (c.1811G>C) pathogenic?

STAG2 p.Arg604Pro (c.1811G>C) is classified Uncertain significance in STAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-26). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1; Associated with Mullegama-Klein-Martinez syndrome.

What condition is associated with STAG2 p.Arg604Pro (c.1811G>C)?

STAG2 p.Arg604Pro (c.1811G>C) is associated with Mullegama-Klein-Martinez syndrome (ClinVar).

How common is STAG2 p.Arg604Pro (c.1811G>C) in the general population?

STAG2 p.Arg604Pro (c.1811G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAG2 p.Arg604Pro (c.1811G>C)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

STAG2 p.Arg604Pro

c.1811G>C · rs1569515797 · VCV3065069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Mullegama-Klein-Martinez syndrome

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic
REVEL	0.665	pathogenic-leaning
SaProt	LLR -10.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 49 kb · p 1.5e-34 · regional, not allelic
Overall
CADD	25.1	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.Arg604Pro
Coding: c.1811G>C
MANE Select: NM_001042750
dbSNP: rs1569515797
Type: single nucleotide variant
Location: chrX:124063195 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 604: 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); a UniProt-annotated variant site (in mkms; uncertain significance)

Full STAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Mullegama-Klein-Martinez syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STAG2 p.Arg604Gln Uncertain significance ★ ⚠ same residue
STAG2 p.Arg604Ter Likely pathogenic ★ same residue
STAG2 p.Arg1033Ter Pathogenic ★★ same condition
STAG2 p.Ala787Gly Uncertain significance ★★ same condition
STAG2 p.Ala787Thr Uncertain significance ★★ ⚠ same condition
STAG2 p.Asn261Ser Uncertain significance ★★ ⚠ same condition
STAG2 p.Thr379Ile Uncertain significance ★★ ⚠ same condition
STAG2 c.1417-39A>C Benign ★★ 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-arg604pro (accessed [today's date]).

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