Is ARSL p.Met61Val (c.181A>G) pathogenic?

ARSL p.Met61Val (c.181A>G) is classified Uncertain significance in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely benign (0.0615); Very rare (popmax 0.00296%, eas).

How common is ARSL p.Met61Val (c.181A>G) in the general population?

ARSL p.Met61Val (c.181A>G) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about ARSL p.Met61Val (c.181A>G)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

ARSL p.Met61Val

c.181A>G · rs952077902 · VCV2500374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.41	donor gain · deltas
Pangolin	Δ0.20	loss · gain 0.04 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP -6.6	GERP -3
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	0.088	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

Grpmax group 0.00296% East Asian · 1/33,826 alleles

Overall 9.11e-05% 1/1,097,897 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.Met61Val
Coding: c.181A>G
MANE Select: NM_000047
dbSNP: rs952077902
Type: single nucleotide variant
Location: chrX:2958278 (GRCh38)
Structure: AlphaFold pLDDT 92.57

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

Similar variants

ARSL c.1289+1G>A Pathogenic/Likely pathogenic ★★ same type
ARSL c.24-2A>G Likely pathogenic ★★ same type
ARSL p.Arg111Cys Likely pathogenic ★★ same type
ARSL p.Gly117Arg Pathogenic/Likely pathogenic ★★ same type
ARSL p.Gly73Ser Likely pathogenic ★★ ⚠ same type
ARSL p.Ala182Thr Uncertain significance ★★ ⚠ same type
ARSL p.Ala251Val Uncertain significance ★★ ⚠ same type
ARSL p.Ala45Val Uncertain significance ★★ ⚠ same type

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-met61val (accessed [today's date]).

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