Is ARSL p.Pro486Ser (c.1456C>T) pathogenic?

ARSL p.Pro486Ser (c.1456C>T) is classified Uncertain significance in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: likely benign (0.2146); Very rare (popmax 0.00351%, sas); Associated with Inborn genetic diseases.

What condition is associated with ARSL p.Pro486Ser (c.1456C>T)?

ARSL p.Pro486Ser (c.1456C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARSL p.Pro486Ser (c.1456C>T) in the general population?

ARSL p.Pro486Ser (c.1456C>T) is very rare (popmax 0.00351%, sas) (gnomAD).

What do computational predictors say about ARSL p.Pro486Ser (c.1456C>T)?

AlphaMissense predicts likely benign (score 0.2146) — an in-silico prediction, not a clinical call.

ARSL p.Pro486Ser

c.1456C>T · rs2089179479 · VCV2540533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00351%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2146	likely benign
REVEL	0.598	indeterminate
SaProt	LLR -11.99	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	22.2	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 0.00351% South Asian · 2/56,915 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000248% 3/1,211,565 alleles · very rare exomes 3/1,097,984 · genomes 0/113,581 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00351%	28,458
Remaining individualsnot grpmax-eligible	0.0021%	47,647

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.Pro486Ser
Coding: c.1456C>T
MANE Select: NM_000047
dbSNP: rs2089179479
Type: single nucleotide variant
Location: chrX:2935146 (GRCh38)
Structure: AlphaFold pLDDT 92.57

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARSL p.Pro486= Likely benign ★ same residue
ARSL p.Glu451Gln Uncertain significance ★★ ⚠ same condition
ARSL p.His259Gln Uncertain significance ★★ ⚠ same condition
ARSL p.Ile40Phe Uncertain significance ★★ ⚠ same condition
ARSL p.Ala35Thr Benign/Likely benign ★★ same condition
ARSL p.Arg420Gln Benign/Likely benign ★★ same condition
ARSL p.Val222Ile Benign/Likely benign ★★ same condition
ARSL p.Ala491Thr 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-pro486ser (accessed [today's date]).

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