Is JAM3 p.Pro142Thr (c.424C>A) pathogenic?

JAM3 p.Pro142Thr (c.424C>A) is classified Uncertain significance in JAM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely pathogenic (0.8984); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with JAM3 p.Pro142Thr (c.424C>A)?

JAM3 p.Pro142Thr (c.424C>A) is associated with Inborn genetic diseases (ClinVar).

How common is JAM3 p.Pro142Thr (c.424C>A) in the general population?

JAM3 p.Pro142Thr (c.424C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JAM3 p.Pro142Thr (c.424C>A)?

AlphaMissense predicts likely pathogenic (score 0.8984) — an in-silico prediction, not a clinical call.

JAM3 p.Pro142Thr

c.424C>A · rs2497294254 · VCV3112201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8984	likely pathogenic
REVEL	0.438	indeterminate
SaProt	LLR -15.02	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 80 kb · p 0.0013 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: JAM3
Protein: p.Pro142Thr
Coding: c.424C>A
MANE Select: NM_032801
dbSNP: rs2497294254
Type: single nucleotide variant
Location: chr11:134144806 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.67
Residue 142: the ig-like c2-type domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

JAM3 p.Ala2Ser Uncertain significance ★★ ⚠ same condition
JAM3 p.Arg107Trp Uncertain significance ★★ same condition
JAM3 p.Arg123Cys Uncertain significance ★★ ⚠ same condition
JAM3 p.Arg14Trp Uncertain significance ★★ ⚠ same condition
JAM3 p.Arg168Gln Uncertain significance ★★ ⚠ same condition
JAM3 p.Arg185Ile Uncertain significance ★★ ⚠ same condition
JAM3 p.Arg191Cys Uncertain significance ★★ ⚠ same condition
JAM3 p.Arg191His 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/jam3-p-pro142thr (accessed [today's date]).

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