Is ARSL p.Ile40Ser (c.119T>G) pathogenic?

ARSL p.Ile40Ser (c.119T>G) is classified Likely pathogenic in ARSL (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-22). AlphaMissense: likely pathogenic (0.8041); Very rare (popmax 0.00175%, afr); Associated with X-linked chondrodysplasia punctata 1.

What condition is associated with ARSL p.Ile40Ser (c.119T>G)?

ARSL p.Ile40Ser (c.119T>G) is associated with X-linked chondrodysplasia punctata 1 (ClinVar).

How common is ARSL p.Ile40Ser (c.119T>G) in the general population?

ARSL p.Ile40Ser (c.119T>G) is very rare (popmax 0.00175%, afr) (gnomAD).

What do computational predictors say about ARSL p.Ile40Ser (c.119T>G)?

AlphaMissense predicts likely pathogenic (score 0.8041) — an in-silico prediction, not a clinical call.

ARSL p.Ile40Ser

c.119T>G · rs80338710 · VCV21031

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked chondrodysplasia punctata 1

Computational evidence

Protein change
AlphaMissense	0.8041	likely pathogenic ✓ concordant with ClinVar
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -15.64	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 8.6	GERP 1.7, phastCons 0.93
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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% African / African-American · 1/57,302 alleles

Overall 0.000892% 1/112,141 alleles · very rare

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: ARSL
Protein: p.Ile40Ser
Coding: c.119T>G
MANE Select: NM_000047
dbSNP: rs80338710
Type: single nucleotide variant
Location: chrX:2958340 (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 p.Ile40Phe Uncertain significance ★★ ⚠ 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
ARSL p.Pro38Leu 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-ile40ser (accessed [today's date]).

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