Is ARSL p.Arg111Pro (c.332G>C) pathogenic?

ARSL p.Arg111Pro (c.332G>C) is classified Pathogenic in ARSL (ClinVar, No assertion criteria, 1 submitter; last evaluated 1995-04-07). AlphaMissense: ambiguous (0.5115); Absent from gnomAD v4.1; Associated with X-linked chondrodysplasia punctata 1.

What condition is associated with ARSL p.Arg111Pro (c.332G>C)?

ARSL p.Arg111Pro (c.332G>C) is associated with X-linked chondrodysplasia punctata 1 (ClinVar).

How common is ARSL p.Arg111Pro (c.332G>C) in the general population?

ARSL p.Arg111Pro (c.332G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSL p.Arg111Pro (c.332G>C)?

AlphaMissense predicts ambiguous (score 0.5115) — an in-silico prediction, not a clinical call.

ARSL p.Arg111Pro

c.332G>C · rs122460153 · VCV11524

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5115 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

X-linked chondrodysplasia punctata 1

Computational evidence

Protein change
AlphaMissense	0.5115	ambiguous
REVEL	0.638	indeterminate
SaProt	LLR -8.01	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	17.8	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

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.Arg111Pro
Coding: c.332G>C
MANE Select: NM_000047
dbSNP: rs122460153
Type: single nucleotide variant
Location: chrX:2953241 (GRCh38)
Structure: AlphaFold pLDDT 92.57
Residue 111: a UniProt-annotated variant site (in cdpx1; significant loss of arylsulfatase activity; no effect on protein stability and localization to the golgi apparatus)

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 p.Arg111Cys Likely pathogenic ★★ same residue
ARSL p.Arg111His Likely pathogenic ★ ⚠ same residue
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

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-arg111pro (accessed [today's date]).

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