Is JAG2 p.Ser204= (c.612C>T) pathogenic?

JAG2 p.Ser204= (c.612C>T) is classified Likely benign in JAG2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-27). Very rare (popmax 0.00534%, afr); Associated with JAG2-related disorder.

What condition is associated with JAG2 p.Ser204= (c.612C>T)?

JAG2 p.Ser204= (c.612C>T) is associated with JAG2-related disorder (ClinVar).

How common is JAG2 p.Ser204= (c.612C>T) in the general population?

JAG2 p.Ser204= (c.612C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

JAG2 p.Ser204=

c.612C>T · rs147352437 · VCV3053714

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

JAG2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -4.1
Overall
CADD	11.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,942 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00198% 32/1,612,410 alleles · very rare exomes 26/1,460,148 · genomes 6/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,736
South Asian	0.0022%	45,509
European (non-Finnish)	0.00212%	47,193
Admixed American	0.00167%	59,942

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: JAG2
Protein: p.Ser204=
Coding: c.612C>T
MANE Select: NM_002226
dbSNP: rs147352437
Type: single nucleotide variant
Location: chr14:105155853 (GRCh38)
Gene constraint: LOEUF 0.495 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 72.90 · 3 PDB
Residue 204: a β-strand; the dsl domain; a UniProt-annotated variant site (in lgmdr27)

Full JAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

JAG2-related disorder

Similar variants

JAG2 p.Arg979Cys Uncertain significance ★★ ⚠ same condition
JAG2 p.Gly530Arg Uncertain significance ★ ⚠ same condition
JAG2 p.Val1103Leu Uncertain significance ★ ⚠ same condition
JAG2 c.1382-6C>T Likely benign same condition
JAG2 c.1429-6G>A Likely benign same condition
JAG2 c.1429-7C>T Likely benign same condition
JAG2 c.1603-7C>T Likely benign same condition
JAG2 c.1753+8G>A Likely benign 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/jag2-p-ser204 (accessed [today's date]).

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