Is JAM3 p.Leu95= (c.285G>A) pathogenic?

JAM3 p.Leu95= (c.285G>A) is classified Benign in JAM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Low-frequency (popmax 3.03%, eas).

How common is JAM3 p.Leu95= (c.285G>A) in the general population?

JAM3 p.Leu95= (c.285G>A) is low-frequency (popmax 3.03%, eas) (gnomAD).

JAM3 p.Leu95=

c.285G>A · rs148009046 · VCV714519

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.03%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.145	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -1.9, phastCons 1
Overall
CADD	8.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.03% East Asian · 1,360/44,884 alleles

Filtering AF 2.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.84%

Overall 0.245% 3,948/1,614,156 alleles · low-frequency exomes 3,464/1,461,864 · genomes 484/152,292 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.25%	31
East Asiangrpmax	3.03%	33
Remaining individualsnot grpmax-eligible	0.29%	345
European (non-Finnish)	0.0252%	3,973
South Asian	0.0242%	4,140
Admixed American	0.0133%	7,502

Finnish 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.Leu95=
Coding: c.285G>A
MANE Select: NM_032801
dbSNP: rs148009046
Type: single nucleotide variant
Location: chr11:134144269 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.67
Residue 95: the ig-like v-type domain

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

Similar variants

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
JAM3 p.Arg191Cys 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-leu95 (accessed [today's date]).

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