Is ARSL p.Arg540Ter (c.1618C>T) pathogenic?

ARSL p.Arg540Ter (c.1618C>T) is classified Pathogenic in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-28). Absent from gnomAD v4.1; Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Arg540Ter (c.1618C>T)?

ARSL p.Arg540Ter (c.1618C>T) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Arg540Ter (c.1618C>T) in the general population?

ARSL p.Arg540Ter (c.1618C>T) is absent from gnomAD v4.1 (gnomAD).

ARSL p.Arg540Ter

c.1618C>T · rs1335931206 · VCV2138468

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

chondrodysplasia punctata, brachytelephalangic, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -2.7
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Arg540Ter
Coding: c.1618C>T
MANE Select: NM_000047
dbSNP: rs1335931206
Type: single nucleotide variant
Location: chrX:2934984 (GRCh38)
Structure: AlphaFold pLDDT 92.57

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

Disease context

chondrodysplasia punctata, brachytelephalangic, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARSL p.Arg540Gly Uncertain significance ★ ⚠ same residue
ARSL p.Arg540= Likely benign ★ same residue
ARSL p.Arg540Gln Likely benign ★ same residue
ARSL c.24-2A>G Likely pathogenic ★★ same condition
ARSL p.Gly73Ser Likely pathogenic ★★ ⚠ same condition
ARSL p.Ala182Thr Uncertain significance ★★ ⚠ same condition
ARSL p.Ala251Val Uncertain significance ★★ ⚠ same condition
ARSL p.Ala45Val 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-arg540ter (accessed [today's date]).

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