Is ARSL p.Ala45= (c.135G>A) pathogenic?

ARSL p.Ala45= (c.135G>A) is classified Likely benign in ARSL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-28). Very rare (popmax 0.00296%, eas); Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Ala45= (c.135G>A)?

ARSL p.Ala45= (c.135G>A) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Ala45= (c.135G>A) in the general population?

ARSL p.Ala45= (c.135G>A) is very rare (popmax 0.00296%, eas) (gnomAD).

ARSL p.Ala45=

c.135G>A · rs144570956 · VCV2870228

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

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 -20	GERP -3.4
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,754 alleles

Filtering AF 0.000907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00071%

Overall 0.00132% 16/1,210,332 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,754
African / African-American	0.00174%	57,313
European (non-Finnish)	0.00156%	63,954

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.Ala45=
Coding: c.135G>A
MANE Select: NM_000047
dbSNP: rs144570956
Type: single nucleotide variant
Location: chrX:2958324 (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.Ala45Val Uncertain significance ★★ ⚠ same residue
ARSL p.Ala45Thr Uncertain significance ★ ⚠ 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.Arg12Ser Uncertain significance ★★ ⚠ same condition
ARSL p.Arg190His 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-ala45 (accessed [today's date]).

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