Is JAM3 p.Phe308Ser (c.923T>C) pathogenic?

JAM3 p.Phe308Ser (c.923T>C) is classified Uncertain significance in JAM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely pathogenic (0.9811); Absent from gnomAD v4.1.

How common is JAM3 p.Phe308Ser (c.923T>C) in the general population?

JAM3 p.Phe308Ser (c.923T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JAM3 p.Phe308Ser (c.923T>C)?

AlphaMissense predicts likely pathogenic (score 0.9811) — an in-silico prediction, not a clinical call.

JAM3 p.Phe308Ser

c.923T>C · rs2120393951 · VCV1485596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9811 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9811	likely pathogenic · top 7% in JAM3
REVEL	0.698	pathogenic-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 80 kb · p 0.0013 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

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.Phe308Ser
Coding: c.923T>C
MANE Select: NM_032801
dbSNP: rs2120393951
Type: single nucleotide variant
Location: chr11:134149171 (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-phe308ser (accessed [today's date]).

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