Is JAM3 p.Arg8Gln (c.23G>A) pathogenic?

JAM3 p.Arg8Gln (c.23G>A) is classified Uncertain significance in JAM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-03). AlphaMissense: likely benign (0.2473); Very rare (popmax 0.00167%, amr).

How common is JAM3 p.Arg8Gln (c.23G>A) in the general population?

JAM3 p.Arg8Gln (c.23G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about JAM3 p.Arg8Gln (c.23G>A)?

AlphaMissense predicts likely benign (score 0.2473) — an in-silico prediction, not a clinical call.

JAM3 p.Arg8Gln

c.23G>A · rs2497161447 · VCV1966957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2473 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2473	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.4, phastCons 0.001
Regional constraint	o/e 1.16	unconstrained · MANE · 80 kb · p 0.0013 · regional, not allelic
Overall
CADD	9.005	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,960 alleles

Overall 6.2e-05% 1/1,612,164 alleles · very rare exomes 1/1,459,818 · genomes 0/152,346 · joint denominator

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.Arg8Gln
Coding: c.23G>A
MANE Select: NM_032801
dbSNP: rs2497161447
Type: single nucleotide variant
Location: chr11:134069106 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.67

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-arg8gln (accessed [today's date]).

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