Is ATRX p.Ser71Phe (c.212C>T) pathogenic?

ATRX p.Ser71Phe (c.212C>T) is classified Uncertain significance in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.1005); Absent from gnomAD v4.1; Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Ser71Phe (c.212C>T)?

ATRX p.Ser71Phe (c.212C>T) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ser71Phe (c.212C>T) in the general population?

ATRX p.Ser71Phe (c.212C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRX p.Ser71Phe (c.212C>T)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

ATRX p.Ser71Phe

c.212C>T · rs2148681475 · VCV2790958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 89 kb · p 0.9 · regional, not allelic
Overall
CADD	19.49	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ser71Phe
Coding: c.212C>T
MANE Select: NM_000489
dbSNP: rs2148681475
Type: single nucleotide variant
Location: chrX:77697613 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 71: the 'disordered' region

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 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
ATRX p.Arg2386Ter 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-ser71phe (accessed [today's date]).

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