Is ATRX p.Ser415= (c.1245C>T) pathogenic?

ATRX p.Ser415= (c.1245C>T) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-12). Ultra-rare (popmax 0.0229%, mid); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Ser415= (c.1245C>T)?

ATRX p.Ser415= (c.1245C>T) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ser415= (c.1245C>T) in the general population?

ATRX p.Ser415= (c.1245C>T) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

ATRX p.Ser415=

c.1245C>T · rs141815992 · VCV700264

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

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 -2.6	GERP -5
Overall
CADD	0.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0229% Middle Eastern · 1/4,363 alleles

Filtering AF 0.00317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00278%

Overall 0.00473% 57/1,205,305 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,363
Finnishnot grpmax-eligible	0.0151%	6,634
Admixed American	0.00875%	11,429
European (non-Finnish)	0.00427%	23,445
Remaining individualsnot grpmax-eligible	0.00422%	23,721
South Asian	0.00353%	28,365
African / African-American	0.00349%	28,619
East Asian	0.00296%	33,777

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.Ser415=
Coding: c.1245C>T
MANE Select: NM_000489
dbSNP: rs141815992
Type: single nucleotide variant
Location: chrX:77684011 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB

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

Disease context

alpha thalassemia-X-linked intellectual disability syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATRX p.Ser415Phe Uncertain significance ★ ⚠ same residue
ATRX p.Ser415Tyr Likely 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

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-ser415 (accessed [today's date]).

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