Is ATRX p.Ser76= (c.228G>A) pathogenic?

ATRX p.Ser76= (c.228G>A) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 9.78%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

ATRX p.Ser76=

Q: What condition is associated with ATRX p.Ser76= (c.228G>A)?

ATRX p.Ser76= (c.228G>A) is associated with Inborn genetic diseases, alpha-thalassemia-myelodysplastic syndrome, alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

Q: How common is ATRX p.Ser76= (c.228G>A) in the general population?

ATRX p.Ser76= (c.228G>A) is common (popmax 9.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.228G>A · rs5959371 · VCV128495

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 9.78%, afr) — too common for a highly-penetrant pathogenic allele

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 -4.4
Overall
CADD	0.154	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.78% African / African-American · 5,577/57,039 alleles

Filtering AF 9.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.48%

Overall 0.513% 6,199/1,208,385 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.78%	10
Remaining individualsnot grpmax-eligible	0.639%	156
Admixed American	0.532%	188
Middle Eastern	0.207%	483
South Asian	0.0177%	5,664
European (non-Finnish)	0.00615%	16,261
East Asian	0.00296%	33,738

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.Ser76=
Coding: c.228G>A
MANE Select: NM_000489
dbSNP: rs5959371
Type: single nucleotide variant
Location: chrX:77697597 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 76: the 'disordered' region

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.Ser76Leu Benign ★ 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-ser76 (accessed [today's date]).

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