Is ARSL p.Pro578Ser (c.1732C>T) pathogenic?

ARSL p.Pro578Ser (c.1732C>T) is classified Likely pathogenic in ARSL (ClinVar, Single submitter, 3 submitters; last evaluated 2026-07-06). AlphaMissense: likely benign (0.2983); Very rare (popmax 0.00893%, sas); Associated with Fetal anomalies with a likely genetic cause.

What condition is associated with ARSL p.Pro578Ser (c.1732C>T)?

ARSL p.Pro578Ser (c.1732C>T) is associated with Fetal anomalies with a likely genetic cause, X-linked chondrodysplasia punctata 1 (ClinVar).

How common is ARSL p.Pro578Ser (c.1732C>T) in the general population?

ARSL p.Pro578Ser (c.1732C>T) is very rare (popmax 0.00893%, sas) (gnomAD).

What do computational predictors say about ARSL p.Pro578Ser (c.1732C>T)?

AlphaMissense predicts likely benign (score 0.2983) — an in-silico prediction, not a clinical call.

ARSL p.Pro578Ser

c.1732C>T · rs28935474 · VCV11528

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2983 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fetal anomalies with a likely genetic cause

Computational evidence

Protein change
AlphaMissense	0.2983	likely benign ⚠ discordant with ClinVar
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -8.46	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	18.55	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 0.00893% South Asian · 5/55,997 alleles

Filtering AF 0.00344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00219%

Overall 0.00046% 5/1,086,229 alleles · very rare

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.Pro578Ser
Coding: c.1732C>T
MANE Select: NM_000047
dbSNP: rs28935474
Type: single nucleotide variant
Location: chrX:2934870 (GRCh38)
Structure: AlphaFold pLDDT 92.57
Residue 578: a UniProt-annotated variant site (in cdpx1)

Full ARSL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fetal anomalies with a likely genetic cause

Also linked: X-linked chondrodysplasia punctata 1

Similar variants

ARSL c.1289+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARSL p.Gly117Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
ARSL p.Gly73Ser Likely pathogenic ★★ same condition
ARSL p.Arg12Ser Uncertain significance ★★ ⚠ same condition
ARSL p.Asp413Glu Uncertain significance ★★ ⚠ same condition
ARSL p.Cys8Ser Uncertain significance ★★ ⚠ same condition
ARSL p.Pro38Leu Uncertain significance ★★ ⚠ same condition
ARSL p.Tyr171Cys 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-pro578ser (accessed [today's date]).

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