Is ATRX p.Ser282= (c.846C>T) pathogenic?

ATRX p.Ser282= (c.846C>T) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-31). Rare (popmax 0.171%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATRX p.Ser282= (c.846C>T)?

ATRX p.Ser282= (c.846C>T) is associated with Inborn genetic diseases, alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ser282= (c.846C>T) in the general population?

ATRX p.Ser282= (c.846C>T) is rare (popmax 0.171%, nfe) (gnomAD).

ATRX p.Ser282=

c.846C>T · rs148015780 · VCV210501

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.171%, nfe)

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 -1.7	GERP -5.2
Overall
CADD	1.803	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.171% European (non-Finnish) · 1,529/894,437 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.161%

Overall 0.138% 1,673/1,209,247 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.171%	585
Remaining individualsnot grpmax-eligible	0.122%	820
Admixed American	0.0765%	1,308
Finnishnot grpmax-eligible	0.0494%	2,025
East Asian	0.0355%	2,815
African / African-American	0.0157%	6,357
South Asian	0.0106%	9,471
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,019

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.Ser282=
Coding: c.846C>T
MANE Select: NM_000489
dbSNP: rs148015780
Type: single nucleotide variant
Location: chrX:77684410 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 282: the add domain; an α-helix

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-X-linked intellectual disability syndrome

Similar variants

ATRX p.Ser282Arg Uncertain significance ⚠ 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
ATRX p.Arg2178Trp 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-ser282 (accessed [today's date]).

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