Is JAM3 p.Arg120Ter (c.358C>T) pathogenic?

JAM3 p.Arg120Ter (c.358C>T) is classified Pathogenic in JAM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Very rare (popmax 0.00329%, sas).

How common is JAM3 p.Arg120Ter (c.358C>T) in the general population?

JAM3 p.Arg120Ter (c.358C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

JAM3 p.Arg120Ter

c.358C>T · rs750102309 · VCV1701178

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.42, phastCons 1
Overall
CADD	37.0	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

Grpmax group 0.00329% South Asian · 3/91,074 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,614,128 alleles · very rare exomes 5/1,461,868 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asiangrpmax	0.00329%	30,358
European (non-Finnish)	8.47e-05%	1,180,020

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: JAM3
Protein: p.Arg120Ter
Coding: c.358C>T
MANE Select: NM_032801
dbSNP: rs750102309
Type: single nucleotide variant
Location: chr11:134144342 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.67
Residue 120: the ig-like v-type domain

Full JAM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

JAM3 p.Arg120Gln Uncertain significance ★ ⚠ same residue
JAM3 c.612+1G>T Pathogenic ★★ same type
JAM3 p.Ala2Ser Uncertain significance ★★ ⚠ same type
JAM3 p.Arg107Trp Uncertain significance ★★ same type
JAM3 p.Arg123Cys Uncertain significance ★★ ⚠ same type
JAM3 p.Arg14Trp Uncertain significance ★★ ⚠ same type
JAM3 p.Arg168Gln Uncertain significance ★★ ⚠ same type
JAM3 p.Arg185Ile Uncertain significance ★★ ⚠ 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/jam3-p-arg120ter (accessed [today's date]).

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