Is ARSL p.Ile53Val (c.157A>G) pathogenic?

ARSL p.Ile53Val (c.157A>G) is classified Benign in ARSL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0633); Common (popmax 9.54%, afr) — too common for a highly-penetrant pathogenic allele; Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Ile53Val (c.157A>G)?

ARSL p.Ile53Val (c.157A>G) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal, connective tissue disorder, X-linked chondrodysplasia punctata 1 (ClinVar).

What do computational predictors say about ARSL p.Ile53Val (c.157A>G)?

AlphaMissense predicts likely benign (score 0.0633) — an in-silico prediction, not a clinical call.

ARSL p.Ile53Val

Q: How common is ARSL p.Ile53Val (c.157A>G) in the general population?

ARSL p.Ile53Val (c.157A>G) is common (popmax 9.54%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.157A>G · rs61733256 · VCV157729

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0633 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.54%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chondrodysplasia punctata, brachytelephalangic, autosomal

Computational evidence

Protein change
AlphaMissense	0.0633	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -3.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	0.001	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.54% African / African-American · 5,457/57,175 alleles

Filtering AF 9.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.25%

Overall 0.547% 6,619/1,210,149 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.54%	10
Middle Eastern	0.919%	109
Remaining individualsnot grpmax-eligible	0.872%	115
Admixed American	0.806%	124
South Asian	0.343%	291
European (non-Finnish)	0.0159%	6,305
East Asian	0.00296%	33,761

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.Ile53Val
Coding: c.157A>G
MANE Select: NM_000047
dbSNP: rs61733256
Type: single nucleotide variant
Location: chrX:2958302 (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: connective tissue disorder 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-ile53val (accessed [today's date]).

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