Is STXBP2 p.Phe97= (c.291C>T) pathogenic?

STXBP2 p.Phe97= (c.291C>T) is classified Likely benign in STXBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-29). Absent from gnomAD v4.1; Associated with familial hemophagocytic lymphohistiocytosis 5.

What condition is associated with STXBP2 p.Phe97= (c.291C>T)?

STXBP2 p.Phe97= (c.291C>T) is associated with familial hemophagocytic lymphohistiocytosis 5 (ClinVar).

How common is STXBP2 p.Phe97= (c.291C>T) in the general population?

STXBP2 p.Phe97= (c.291C>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

STXBP2 p.Phe97=

c.291C>T · rs1246771714 · VCV2854118

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial hemophagocytic lymphohistiocytosis 5

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 0.52	GERP -3.5, phastCons 1
Overall
CADD	7.605	PHRED · no single calibrated threshold — expert panels disagree

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: STXBP2
Protein: p.Phe97=
Coding: c.291C>T
MANE Select: NM_006949
dbSNP: rs1246771714
Type: single nucleotide variant
Location: chr19:7640775 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.41 · 1 PDB

Full STXBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial hemophagocytic lymphohistiocytosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hemophagocytic lymphohistiocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Infancy
Prevalence: 1-9 / 100 000 (Sweden)

Similar variants

STXBP2 p.Phe97Leu Uncertain significance ★ ⚠ same residue
STXBP2 c.1107+1G>C Likely pathogenic ★★ same condition
STXBP2 c.1247-1G>C Pathogenic ★★ same condition
STXBP2 c.1356+1G>T Likely pathogenic ★★ same condition
STXBP2 c.169+2T>G Pathogenic/Likely pathogenic ★★ same condition
STXBP2 c.247-2A>C Likely pathogenic ★★ same condition
STXBP2 c.247-2A>G Likely pathogenic ★★ same condition
STXBP2 c.87+2T>C Pathogenic/Likely pathogenic ★★ 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/stxbp2-p-phe97 (accessed [today's date]).

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