Is STAG2 p.Phe367= (c.1101T>C) pathogenic?

STAG2 p.Phe367= (c.1101T>C) is classified Benign/Likely benign in STAG2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-19). Ultra-rare (popmax 0.0629%, eas); Associated with Mullegama-Klein-Martinez syndrome.

What condition is associated with STAG2 p.Phe367= (c.1101T>C)?

STAG2 p.Phe367= (c.1101T>C) is associated with Mullegama-Klein-Martinez syndrome, holoprosencephaly 13, X-linked (ClinVar).

How common is STAG2 p.Phe367= (c.1101T>C) in the general population?

STAG2 p.Phe367= (c.1101T>C) is ultra-rare (popmax 0.0629%, eas) (gnomAD).

STAG2 p.Phe367=

c.1101T>C · rs190643141 · VCV1612997

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0629%, eas)

Conditions

Mullegama-Klein-Martinez syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 1
Overall
CADD	9.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0629% East Asian · 21/33,378 alleles

Filtering AF 0.0422% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0354%

Overall 0.00186% 22/1,183,485 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0629%	1,589
Remaining individualsnot grpmax-eligible	0.00214%	46,620

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: STAG2
Protein: p.Phe367=
Coding: c.1101T>C
MANE Select: NM_001042750
dbSNP: rs190643141
Type: single nucleotide variant
Location: chrX:124051204 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 367: the scd domain; 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); an α-helix

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

Also linked: holoprosencephaly 13, X-linked

Similar variants

STAG2 p.Arg1012Ter Pathogenic ★★ same condition
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.Met1180Val 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-phe367 (accessed [today's date]).

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