Is ARSL p.Asp46= (c.138C>T) pathogenic?

ARSL p.Asp46= (c.138C>T) is classified Likely benign in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). Ultra-rare (popmax 0.0734%, afr); Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Asp46= (c.138C>T)?

ARSL p.Asp46= (c.138C>T) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Asp46= (c.138C>T) in the general population?

ARSL p.Asp46= (c.138C>T) is ultra-rare (popmax 0.0734%, afr) (gnomAD).

ARSL p.Asp46=

c.138C>T · rs772470238 · VCV2061379

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, 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 -5.5	GERP -3
Overall
CADD	0.435	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0734% African / African-American · 42/57,252 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0496%

Overall 0.00512% 62/1,210,278 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0734%	1,363
East Asian	0.0148%	6,754
Remaining individualsnot grpmax-eligible	0.00841%	11,897
Admixed American	0.00218%	45,768
European (non-Finnish)	0.00112%	89,534

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.Asp46=
Coding: c.138C>T
MANE Select: NM_000047
dbSNP: rs772470238
Type: single nucleotide variant
Location: chrX:2958321 (GRCh38)
Structure: AlphaFold pLDDT 92.57
Residue 46: 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-asp46 (accessed [today's date]).

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