Is ARSL p.Pro499= (c.1497G>A) pathogenic?

ARSL p.Pro499= (c.1497G>A) is classified Likely benign in ARSL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-25). Ultra-rare (popmax 0.0821%, afr); Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Pro499= (c.1497G>A)?

ARSL p.Pro499= (c.1497G>A) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Pro499= (c.1497G>A) in the general population?

ARSL p.Pro499= (c.1497G>A) is ultra-rare (popmax 0.0821%, afr) (gnomAD).

ARSL p.Pro499=

c.1497G>A · rs75821383 · VCV2729141

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0821%, afr)

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 -2.7
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0821% African / African-American · 47/57,217 alleles

Filtering AF 0.0635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0568%

Overall 0.0086% 104/1,209,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0821%	1,217
Finnishnot grpmax-eligible	0.0322%	3,105
Remaining individualsnot grpmax-eligible	0.0126%	7,934
Admixed American	0.0109%	9,135
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,031
European (non-Finnish)	0.00324%	30,868
South Asian	0.00176%	56,722

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.Pro499=
Coding: c.1497G>A
MANE Select: NM_000047
dbSNP: rs75821383
Type: single nucleotide variant
Location: chrX:2935105 (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.Pro499Leu 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-pro499 (accessed [today's date]).

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