Is JAM3 p.His196= (c.588C>T) pathogenic?

JAM3 p.His196= (c.588C>T) is classified Likely benign in JAM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-23). Absent from gnomAD v4.1.

How common is JAM3 p.His196= (c.588C>T) in the general population?

JAM3 p.His196= (c.588C>T) is absent from gnomAD v4.1 (gnomAD).

JAM3 p.His196=

c.588C>T · rs1304664976 · VCV728403

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.007	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP 0.24, phastCons 0.016
Overall
CADD	3.93	PHRED · no single calibrated threshold — expert panels disagree

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.His196=
Coding: c.588C>T
MANE Select: NM_032801
dbSNP: rs1304664976
Type: single nucleotide variant
Location: chr11:134144970 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.67
Residue 196: the ig-like c2-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-his196 (accessed [today's date]).

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