Is ARSL p.Ser31Arg (c.91A>C) pathogenic?

ARSL p.Ser31Arg (c.91A>C) is classified Uncertain significance in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.0952); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARSL p.Ser31Arg (c.91A>C)?

ARSL p.Ser31Arg (c.91A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ARSL p.Ser31Arg (c.91A>C) in the general population?

ARSL p.Ser31Arg (c.91A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSL p.Ser31Arg (c.91A>C)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

ARSL p.Ser31Arg

c.91A>C · VCV3316705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -7.12	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 -8.4	GERP -2.2
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARSL
Protein: p.Ser31Arg
Coding: c.91A>C
MANE Select: NM_000047
Type: single nucleotide variant
Location: chrX:2958368 (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.Ser31= 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-ser31arg (accessed [today's date]).

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