Is ATRX p.Asp2136Asn (c.6406G>A) pathogenic?

ATRX p.Asp2136Asn (c.6406G>A) is classified Conflicting classifications of pathogenicity in ATRX (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-28). AlphaMissense: likely pathogenic (0.9982); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ATRX p.Asp2136Asn (c.6406G>A)?

ATRX p.Asp2136Asn (c.6406G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ATRX p.Asp2136Asn (c.6406G>A) in the general population?

ATRX p.Asp2136Asn (c.6406G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRX p.Asp2136Asn (c.6406G>A)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

ATRX p.Asp2136Asn

c.6406G>A · rs2064896365 · VCV985028

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,202,377)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic · top 7% in ATRX
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -13.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.10	constrained · MANE · 1,315 bp · p 2.3e-15 · regional, not allelic
Overall
CADD	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,202,377). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATRX
Protein: p.Asp2136Asn
Coding: c.6406G>A
MANE Select: NM_000489
dbSNP: rs2064896365
Type: single nucleotide variant
Location: chrX:77558767 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 2136: the 'interaction with mecp2' region; the helicase c-terminal domain

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

Similar variants

ATRX p.Asp2136= Likely benign ★ same residue
ATRX p.Arg246Cys Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg37Ter Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Asn247Ser Likely pathogenic ★★ same condition
ATRX p.Cys220Tyr Pathogenic/Likely pathogenic ★★ same condition
ATRX c.4121-3A>G Uncertain significance ★★ same condition
ATRX c.6326+3A>G Uncertain significance ★★ same condition
ATRX p.Ala2356Val Uncertain significance ★★ ⚠ 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-asp2136asn (accessed [today's date]).

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