Is ARSL p.Arg183= (c.549C>T) pathogenic?

ARSL p.Arg183= (c.549C>T) is classified Benign in ARSL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-31). Common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Arg183= (c.549C>T)?

ARSL p.Arg183= (c.549C>T) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal, connective tissue disorder, X-linked chondrodysplasia punctata 1 (ClinVar).

ARSL p.Arg183=

Q: How common is ARSL p.Arg183= (c.549C>T) in the general population?

ARSL p.Arg183= (c.549C>T) is common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.549C>T · rs5982618 · VCV157735

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 10.8%, afr) — 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 -0.93	GERP -2.7
Overall
CADD	1.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.8% African / African-American · 6,138/56,827 alleles

Filtering AF 10.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.5%

Overall 0.689% 8,335/1,209,080 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.8%	9
Middle Eastern	2.11%	47
Admixed American	1.19%	84
Remaining individualsnot grpmax-eligible	1.1%	91
Ashkenazi Jewishnot grpmax-eligible	0.44%	227
European (non-Finnish)	0.102%	983
South Asian	0.0476%	2,099
East Asian	0.00593%	16,850
Finnishnot grpmax-eligible	0.00215%	46,514

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.Arg183=
Coding: c.549C>T
MANE Select: NM_000047
dbSNP: rs5982618
Type: single nucleotide variant
Location: chrX:2949609 (GRCh38)
Structure: AlphaFold pLDDT 92.57
Residue 183: a UniProt-annotated variant site (in)

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

Also linked: connective tissue disorder X-linked chondrodysplasia punctata 1

Similar variants

ARSL p.Arg183His Benign/Likely benign ★★ same residue
ARSL c.1289+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARSL c.24-2A>G Likely pathogenic ★★ same condition
ARSL p.Gly117Arg Pathogenic/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-arg183 (accessed [today's date]).

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