Is ARSB p.Thr224Ser (c.671C>G) pathogenic?

ARSB p.Thr224Ser (c.671C>G) is classified Uncertain significance in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0735); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with ARSB p.Thr224Ser (c.671C>G)?

ARSB p.Thr224Ser (c.671C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARSB p.Thr224Ser (c.671C>G) in the general population?

ARSB p.Thr224Ser (c.671C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ARSB p.Thr224Ser (c.671C>G)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

ARSB p.Thr224Ser

c.671C>G · VCV4585608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -4.81	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 4.4	GERP 0.12, phastCons 1
Overall
CADD	17.39	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 6.84e-05%

Overall 6.84e-05% 1/1,461,678 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: ARSB
Protein: p.Thr224Ser
Coding: c.671C>G
MANE Select: NM_020427 · reported on NM_000046
Type: single nucleotide variant
Location: chr5:78964435 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB

Full ARSB 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

ARSB p.Thr224Ile Uncertain significance ⚠ same residue
ARSB p.Gly324Val Pathogenic/Likely pathogenic ★★ same condition
ARSB p.Arg180His Uncertain significance ★★ ⚠ same condition
ARSB p.Asn225Lys Uncertain significance ★★ ⚠ same condition
ARSB p.Asn262Asp Uncertain significance ★★ ⚠ same condition
ARSB p.Asp416Val Uncertain significance ★★ ⚠ same condition
ARSB p.Gly309Ser Uncertain significance ★★ ⚠ same condition
ARSB p.Pro10Leu 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/arsb-p-thr224ser (accessed [today's date]).

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