Is ARSL p.Thr63Ile (c.188C>T) pathogenic?

ARSL p.Thr63Ile (c.188C>T) is classified Uncertain significance in ARSL (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.7806); Absent from gnomAD v4.1; Associated with X-linked chondrodysplasia punctata 1.

What condition is associated with ARSL p.Thr63Ile (c.188C>T)?

ARSL p.Thr63Ile (c.188C>T) is associated with X-linked chondrodysplasia punctata 1 (ClinVar).

How common is ARSL p.Thr63Ile (c.188C>T) in the general population?

ARSL p.Thr63Ile (c.188C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSL p.Thr63Ile (c.188C>T)?

AlphaMissense predicts likely pathogenic (score 0.7806) — an in-silico prediction, not a clinical call.

ARSL p.Thr63Ile

c.188C>T · VCV3382301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7806 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked chondrodysplasia punctata 1

Computational evidence

Protein change
AlphaMissense	0.7806	likely pathogenic
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -13.26	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 9.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	22.3	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

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: ARSL
Protein: p.Thr63Ile
Coding: c.188C>T
MANE Select: NM_000047
Type: single nucleotide variant
Location: chrX:2955535 (GRCh38)
Structure: AlphaFold pLDDT 92.57

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

Disease context

X-linked chondrodysplasia punctata 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARSL c.1289+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARSL p.Gly117Arg Pathogenic/Likely pathogenic ★★ same condition
ARSL p.Gly73Ser Likely pathogenic ★★ ⚠ same condition
ARSL p.Arg12Ser Uncertain significance ★★ ⚠ same condition
ARSL p.Asp413Glu Uncertain significance ★★ ⚠ same condition
ARSL p.Cys8Ser Uncertain significance ★★ ⚠ same condition
ARSL p.Pro38Leu Uncertain significance ★★ ⚠ same condition
ARSL p.Tyr171Cys 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/arsl-p-thr63ile (accessed [today's date]).

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