Is ARSL p.Val227Phe (c.679G>T) pathogenic?

ARSL p.Val227Phe (c.679G>T) is classified Uncertain significance in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.1742); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARSL p.Val227Phe (c.679G>T)?

ARSL p.Val227Phe (c.679G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARSL p.Val227Phe (c.679G>T) in the general population?

ARSL p.Val227Phe (c.679G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSL p.Val227Phe (c.679G>T)?

AlphaMissense predicts likely benign (score 0.1742) — an in-silico prediction, not a clinical call.

ARSL p.Val227Phe

c.679G>T · VCV3949643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1742 · 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	0.1742	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -7.57	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 -1.4	GERP -3
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	3.006	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.Val227Phe
Coding: c.679G>T
MANE Select: NM_000047
Type: single nucleotide variant
Location: chrX:2949479 (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.Val227= 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-val227phe (accessed [today's date]).

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