Is ARX p.Ser486Phe (c.1457C>T) pathogenic?

ARX p.Ser486Phe (c.1457C>T) is classified Uncertain significance in ARX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.9836); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARX p.Ser486Phe (c.1457C>T)?

ARX p.Ser486Phe (c.1457C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARX p.Ser486Phe (c.1457C>T) in the general population?

ARX p.Ser486Phe (c.1457C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Ser486Phe (c.1457C>T)?

AlphaMissense predicts likely pathogenic (score 0.9836) — an in-silico prediction, not a clinical call.

ARX p.Ser486Phe

c.1457C>T · VCV3901522

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9836 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,134,436)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9836	likely pathogenic
REVEL	0.768	pathogenic-leaning
SaProt	LLR -10.92	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,715 bp · p 0.00019 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,134,436). 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: ARX
Protein: p.Ser486Phe
Coding: c.1457C>T
MANE Select: NM_139058
Type: single nucleotide variant
Location: chrX:25004902 (GRCh38)
Structure: AlphaFold pLDDT 56.51

Full ARX 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

ARX p.Glu308Ter Pathogenic ★★ same condition
ARX c.196+6G>A Uncertain significance ★★ same condition
ARX p.Ala149Val Uncertain significance ★★ ⚠ same condition
ARX p.Arg204Cys Uncertain significance ★★ ⚠ same condition
ARX p.Gly34Ala Uncertain significance ★★ ⚠ same condition
ARX p.Leu159Phe Uncertain significance ★★ ⚠ same condition
ARX p.Pro135Leu Uncertain significance ★★ ⚠ same condition
ARX p.Ser31Arg 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/arx-p-ser486phe (accessed [today's date]).

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