Is ARSK p.Ile367Phe (c.1099A>T) pathogenic?

ARSK p.Ile367Phe (c.1099A>T) is classified Uncertain significance in ARSK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.127); Absent from gnomAD v4.1.

How common is ARSK p.Ile367Phe (c.1099A>T) in the general population?

ARSK p.Ile367Phe (c.1099A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSK p.Ile367Phe (c.1099A>T)?

AlphaMissense predicts likely benign (score 0.127) — an in-silico prediction, not a clinical call.

ARSK p.Ile367Phe

c.1099A>T · VCV4149880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.127 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.127	likely benign
REVEL	0.645	pathogenic-leaning
SaProt	LLR -6.72	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	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.24 · regional, not allelic
Overall
CADD	22.6	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

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: ARSK
Protein: p.Ile367Phe
Coding: c.1099A>T
MANE Select: NM_198150
Type: single nucleotide variant
Location: chr5:95600849 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.50
Residue 367: a UniProt-annotated variant site (in mps10; mutant protein is not detected by western blot in transfected cells; severely decreased glucuronate-2-sulfatase activity)

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

Similar variants

ARSK p.Lys518= Benign/Likely benign ★★ same type
ARSK p.Ala11Thr Uncertain significance ★ ⚠ same type
ARSK p.Ala191Pro Uncertain significance ★ ⚠ same type
ARSK p.Ala238Asp Uncertain significance ★ ⚠ same type
ARSK p.Ala318Thr Uncertain significance ★ ⚠ same type
ARSK p.Ala428Gly Uncertain significance ★ ⚠ same type
ARSK p.Arg122Gln Uncertain significance ★ ⚠ same type
ARSK p.Arg141Leu 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/arsk-p-ile367phe (accessed [today's date]).

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