Is ATRX p.Pro190= (c.570T>G) pathogenic?

ATRX p.Pro190= (c.570T>G) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Rare (popmax 0.411%, amr); Associated with Inborn genetic diseases.

How common is ATRX p.Pro190= (c.570T>G) in the general population?

ATRX p.Pro190= (c.570T>G) is rare (popmax 0.411%, amr) (gnomAD).

ATRX p.Pro190=

Q: What condition is associated with ATRX p.Pro190= (c.570T>G)?

ATRX p.Pro190= (c.570T>G) is associated with Inborn genetic diseases, alpha-thalassemia-myelodysplastic syndrome, alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

c.570T>G · rs188831993 · VCV93142

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.411%, amr)

Conditions

Inborn genetic diseases

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 7.9	GERP 1.4, phastCons 1
Overall
CADD	12.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.411% Admixed American · 188/45,781 alleles

Filtering AF 0.363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.344%

Overall 0.0159% 192/1,205,934 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.411%	244
African / African-American	0.00524%	19,087
European (non-Finnish)	0.000112%	891,448

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: ATRX
Protein: p.Pro190=
Coding: c.570T>G
MANE Select: NM_000489
dbSNP: rs188831993
Type: single nucleotide variant
Location: chrX:77688842 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 190: the add domain; a UniProt-annotated variant site (in atrx); a UniProt-annotated variant site (in atrx; impairs interaction with histone h3 peptides and reduces localization to pericentromeric heterochromatin foci); a turn

Full ATRX 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

Also linked: alpha-thalassemia-myelodysplastic syndrome alpha thalassemia-X-linked intellectual disability syndrome intellectual disability-hypotonic facies syndrome, X-linked, 1

Similar variants

ATRX p.Pro190Ala Likely pathogenic ★ same residue
ATRX p.Pro190Leu Likely pathogenic ★ same residue
ATRX c.5449-7A>G Likely pathogenic ★★ same condition
ATRX p.Arg1022Ter Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg1661Cys Likely pathogenic ★★ ⚠ same condition
ATRX p.Arg2085Cys Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg2131Gln Pathogenic/Likely pathogenic ★★ 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/atrx-p-pro190 (accessed [today's date]).

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