Is ARSL p.Ala26= (c.78A>G) pathogenic?

ARSL p.Ala26= (c.78A>G) is classified Benign in ARSL (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). Common (popmax 22.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

ARSL p.Ala26=

Q: What condition is associated with ARSL p.Ala26= (c.78A>G)?

ARSL p.Ala26= (c.78A>G) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal, X-linked chondrodysplasia punctata 1 (ClinVar).

Q: How common is ARSL p.Ala26= (c.78A>G) in the general population?

ARSL p.Ala26= (c.78A>G) is common (popmax 22.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.78A>G · rs35718384 · VCV157737

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 22.8%, 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 -0.3	GERP -0.88
Overall
CADD	2.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.8% African / African-American · 13,009/57,122 alleles

Filtering AF 22.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.3%

Overall 1.29% 15,579/1,210,324 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.8%	4
Remaining individualsnot grpmax-eligible	1.93%	52
Admixed American	1.58%	63
Middle Eastern	1.29%	78
South Asian	0.561%	178
East Asian	0.166%	603
European (non-Finnish)	0.0551%	1,816

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.Ala26=
Coding: c.78A>G
MANE Select: NM_000047
dbSNP: rs35718384
Type: single nucleotide variant
Location: chrX:2958381 (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

Also linked: X-linked chondrodysplasia punctata 1

Similar variants

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
ARSL p.Arg12Ser 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-ala26 (accessed [today's date]).

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