Is ATRX p.Arg1503Ser (c.4509A>T) pathogenic?

ATRX p.Arg1503Ser (c.4509A>T) is classified Likely pathogenic in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2015-12-09). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1.

How common is ATRX p.Arg1503Ser (c.4509A>T) in the general population?

ATRX p.Arg1503Ser (c.4509A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRX p.Arg1503Ser (c.4509A>T)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

ATRX p.Arg1503Ser

c.4509A>T · rs1057517997 · VCV372813

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 3% in ATRX
REVEL	0.263	benign-leaning
SaProt	LLR -15.75	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.57	GERP -4.7, phastCons 0.024
Regional constraint	o/e 0.24	constrained · MANE · 19 kb · p 1.7e-15 · regional, not allelic
Overall
CADD	16.83	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATRX
Protein: p.Arg1503Ser
Coding: c.4509A>T
MANE Select: NM_000489
dbSNP: rs1057517997
Type: single nucleotide variant
Location: chrX:77652162 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB

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

Similar variants

ATRX c.134-2A>G Pathogenic/Likely pathogenic ★★ same type
ATRX c.5449-7A>G Likely pathogenic ★★ same type
ATRX p.Arg1022Ter Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg1661Cys Likely pathogenic ★★ ⚠ same type
ATRX p.Arg2085Cys Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg2131Gln Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg2178Trp Pathogenic/Likely pathogenic ★★ same type

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-arg1503ser (accessed [today's date]).

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