Is JARID2 p.Pro558= (c.1674C>T) pathogenic?

JARID2 p.Pro558= (c.1674C>T) is classified Likely benign in JARID2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-19). Ultra-rare (popmax 0.0415%, afr); Associated with JARID2-related disorder.

What condition is associated with JARID2 p.Pro558= (c.1674C>T)?

JARID2 p.Pro558= (c.1674C>T) is associated with JARID2-related disorder (ClinVar).

How common is JARID2 p.Pro558= (c.1674C>T) in the general population?

JARID2 p.Pro558= (c.1674C>T) is ultra-rare (popmax 0.0415%, afr) (gnomAD).

JARID2 p.Pro558=

c.1674C>T · rs376937633 · VCV3041087

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0415%, afr)

Conditions

JARID2-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 -6.3	GERP -3.5
Overall
CADD	2.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0415% African / African-American · 31/74,768 alleles

Filtering AF 0.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0261%

Overall 0.015% 240/1,601,066 alleles · ultra-rare exomes 214/1,448,812 · genomes 26/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0415%	2,412
South Asian	0.0391%	2,559
European (non-Finnish)	0.0145%	6,892
Remaining individualsnot grpmax-eligible	0.00485%	20,614
Admixed American	0.00168%	59,440

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: JARID2
Protein: p.Pro558=
Coding: c.1674C>T
MANE Select: NM_004973
dbSNP: rs376937633
Type: single nucleotide variant
Location: chr6:15496899 (GRCh38)
Gene constraint: LOEUF 0.202 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 62.74 · 17 PDB
Residue 558: the jmjn domain

Full JARID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

JARID2-related disorder

Similar variants

JARID2 p.Arg311Gly Uncertain significance ★★ ⚠ same condition
JARID2 p.Thr1043Ser Uncertain significance ★★ ⚠ same condition
JARID2 p.Asn1194Ser Uncertain significance ★ ⚠ same condition
JARID2 p.Leu163Pro Uncertain significance ★ ⚠ same condition
JARID2 p.Lys131Asn Uncertain significance ★ ⚠ same condition
JARID2 p.Lys775Glu Uncertain significance ★ ⚠ same condition
JARID2 p.Pro843Leu Uncertain significance ★ ⚠ same condition
JARID2 p.Ser18Asn 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/jarid2-p-pro558 (accessed [today's date]).

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