Is ARSL p.Pro576= (c.1728G>A) pathogenic?

ARSL p.Pro576= (c.1728G>A) is classified Benign in ARSL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 8.62%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Pro576= (c.1728G>A)?

ARSL p.Pro576= (c.1728G>A) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

ARSL p.Pro576=

Q: How common is ARSL p.Pro576= (c.1728G>A) in the general population?

ARSL p.Pro576= (c.1728G>A) is common (popmax 8.62%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1728G>A · rs11055 · VCV157731

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 8.62%, nfe) — too common for a highly-penetrant pathogenic allele

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 -13	GERP -2.7
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.62% European (non-Finnish) · 75,327/873,367 alleles

Filtering AF 8.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.55%

Overall 7.23% 85,489/1,182,636 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	8.62%	12
Finnishnot grpmax-eligible	6.86%	15
Remaining individualsnot grpmax-eligible	6.46%	15
Ashkenazi Jewishnot grpmax-eligible	6.35%	16
Middle Eastern	4.36%	23
Amishnot grpmax-eligible	3.52%	28
Admixed American	2.86%	35
African / African-American	1.14%	87
South Asian	0.912%	110
East Asian	0.0179%	5,597

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.Pro576=
Coding: c.1728G>A
MANE Select: NM_000047
dbSNP: rs11055
Type: single nucleotide variant
Location: chrX:2934874 (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.Pro576Leu 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.Ala45Val 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-pro576 (accessed [today's date]).

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