Is ARSL p.Lys378= (c.1134G>A) pathogenic?

ARSL p.Lys378= (c.1134G>A) is classified Likely benign in ARSL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-13). Very rare (popmax 9.11e-05%); Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Lys378= (c.1134G>A)?

ARSL p.Lys378= (c.1134G>A) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Lys378= (c.1134G>A) in the general population?

ARSL p.Lys378= (c.1134G>A) is very rare (popmax 9.11e-05%) (gnomAD).

ARSL p.Lys378=

c.1134G>A · rs2089231820 · VCV2040222

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

Conditions

chondrodysplasia punctata, brachytelephalangic, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -2.6, phastCons 1
Overall
CADD	0.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.11e-05%

Overall 9.11e-05% 1/1,097,941 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.Lys378=
Coding: c.1134G>A
MANE Select: NM_000047
dbSNP: rs2089231820
Type: single nucleotide variant
Location: chrX:2938250 (GRCh38)
Structure: AlphaFold pLDDT 92.57
Residue 378: a binding site

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 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
ARSL p.Arg12Ser Uncertain significance ★★ ⚠ same condition
ARSL p.Arg190His Uncertain significance ★★ ⚠ same condition
ARSL p.Asp413Glu 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-lys378 (accessed [today's date]).

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