Is JAG2 p.Phe407fs (c.1219_1225del) pathogenic?

JAG2 p.Phe407fs (c.12191225del) is classified Pathogenic in JAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). No gnomAD frequency available for this variant; Associated with muscular dystrophy, limb-girdle, autosomal recessive 27.

What condition is associated with JAG2 p.Phe407fs (c.1219_1225del)?

JAG2 p.Phe407fs (c.1219_1225del) is associated with muscular dystrophy, limb-girdle, autosomal recessive 27 (ClinVar).

How common is JAG2 p.Phe407fs (c.1219_1225del) in the general population?

JAG2 p.Phe407fs (c.1219_1225del) is no gnomAD frequency available for this variant (gnomAD).

JAG2 p.Phe407fs

c.1219_1225del · rs2140979845 · VCV1527878

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

muscular dystrophy, limb-girdle, autosomal recessive 27

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: JAG2
Protein: p.Phe407fs
Coding: c.1219_1225del
MANE Select: NM_002226
dbSNP: rs2140979845
Type: Deletion
Location: chr14:105151325 (GRCh38)
Gene constraint: LOEUF 0.495 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 72.90 · 3 PDB
Residue 407: the egf-like 5; calcium-binding domain; a UniProt-annotated variant site (in lgmdr27)

Full JAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

muscular dystrophy, limb-girdle, autosomal recessive 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

JAG2 p.Pro854_Gly856del Uncertain significance same condition
JAG2 p.Gly839Arg Likely pathogenic ★★ same condition
JAG2 p.Arg165Ter Likely pathogenic ★ same condition
JAG2 p.Gly281Cys Likely pathogenic ★ same condition
JAG2 p.Tyr104Ter Likely pathogenic ★ same condition
JAG2 p.Ala243Asp Uncertain significance ★ ⚠ same condition
JAG2 p.Arg712Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
JAG2 p.Arg735Cys 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/jag2-p-phe407fs (accessed [today's date]).

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