Is ATRX p.Val277= (c.831C>T) pathogenic?

ATRX p.Val277= (c.831C>T) is classified Conflicting classifications of pathogenicity in ATRX (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-27). Rare (popmax 0.137%, mid); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Val277= (c.831C>T)?

ATRX p.Val277= (c.831C>T) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Val277= (c.831C>T) in the general population?

ATRX p.Val277= (c.831C>T) is rare (popmax 0.137%, mid) (gnomAD).

ATRX p.Val277=

c.831C>T · rs142561199 · VCV281970

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.137%, 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 1.8	GERP -3.3, phastCons 1
Overall
CADD	4.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.137% Middle Eastern · 6/4,372 alleles

Filtering AF 0.0598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0408%

Overall 0.00967% 117/1,210,086 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.137%	729
Remaining individualsnot grpmax-eligible	0.0231%	4,326
Admixed American	0.0109%	9,153
European (non-Finnish)	0.0106%	9,422

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.Val277=
Coding: c.831C>T
MANE Select: NM_000489
dbSNP: rs142561199
Type: single nucleotide variant
Location: chrX:77684425 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 277: the add domain; an α-helix

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.Val277Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ATRX p.Val277Gly 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

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-val277 (accessed [today's date]).

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