Is JAM2 p.Met1Val (c.1A>G) pathogenic?

JAM2 p.Met1Val (c.1A>G) is classified Pathogenic in JAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-27). Absent from gnomAD v4.1; Associated with basal ganglia calcification, idiopathic, 8, autosomal recessive.

What condition is associated with JAM2 p.Met1Val (c.1A>G)?

JAM2 p.Met1Val (c.1A>G) is associated with basal ganglia calcification, idiopathic, 8, autosomal recessive (ClinVar).

How common is JAM2 p.Met1Val (c.1A>G) in the general population?

JAM2 p.Met1Val (c.1A>G) is absent from gnomAD v4.1 (gnomAD).

How is Bilateral striopallidodentate calcinosis inherited?

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

JAM2 p.Met1Val

c.1A>G · rs1600978441 · VCV829533

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

basal ganglia calcification, idiopathic, 8, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.287	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: JAM2
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_021219
dbSNP: rs1600978441
Type: single nucleotide variant
Location: chr21:25639822 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 82.91

Full JAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

basal ganglia calcification, idiopathic, 8, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bilateral striopallidodentate calcinosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Adult

Similar variants

JAM2 p.Arg229Ter Pathogenic ★★ same condition
JAM2 p.Arg108His Pathogenic ⚠ same condition
JAM2 p.Trp168Cys Pathogenic same condition
JAM2 c.395-1dup Pathogenic same condition
JAM2 c.(67+1_68-1 Pathogenic same condition
JAM2 p.Ile47_Leu48insTer Pathogenic same condition
JAM2 p.Ser59_Arg60insTer Pathogenic same condition
JAM2 c.68-96C>A Benign ★★ same type

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/jam2-p-met1val (accessed [today's date]).

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