Is ARSL p.Thr409= (c.1227G>A) pathogenic?

ARSL p.Thr409= (c.1227G>A) is classified Likely benign in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-25). Very rare (popmax 0.00348%, afr); Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Thr409= (c.1227G>A)?

ARSL p.Thr409= (c.1227G>A) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Thr409= (c.1227G>A) in the general population?

ARSL p.Thr409= (c.1227G>A) is very rare (popmax 0.00348%, afr) (gnomAD).

ARSL p.Thr409=

c.1227G>A · rs369695084 · VCV2147109

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00348%, 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 -1.8	GERP -2.8
Overall
CADD	0.378	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00348% African / African-American · 2/57,391 alleles

Filtering AF 0.000578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000216%

Overall 0.000578% 7/1,210,527 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00348%	28,695
Admixed American	0.00218%	45,855
Remaining individualsnot grpmax-eligible	0.0021%	47,593
European (non-Finnish)	0.000335%	298,453

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.Thr409=
Coding: c.1227G>A
MANE Select: NM_000047
dbSNP: rs369695084
Type: single nucleotide variant
Location: chrX:2938157 (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.Thr409Met Likely pathogenic ★ ⚠ same residue
ARSL p.Thr409Arg 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

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-thr409 (accessed [today's date]).

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