Is ARSB p.Thr92Ala (c.274A>G) pathogenic?

ARSB p.Thr92Ala (c.274A>G) is classified Uncertain significance in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). AlphaMissense: likely pathogenic (0.7552); Absent from gnomAD v4.1.

How common is ARSB p.Thr92Ala (c.274A>G) in the general population?

ARSB p.Thr92Ala (c.274A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSB p.Thr92Ala (c.274A>G)?

AlphaMissense predicts likely pathogenic (score 0.7552) — an in-silico prediction, not a clinical call.

ARSB p.Thr92Ala

c.274A>G · rs2530667465 · VCV2581446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7552 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,513,422)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7552	likely pathogenic
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.7, phastCons 1
Overall
CADD	26.2	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

No allele count reported in gnomAD v4.1 (AN 1,513,422). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARSB
Protein: p.Thr92Ala
Coding: c.274A>G
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs2530667465
Type: single nucleotide variant
Location: chr5:78984975 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB
Residue 92: a β-strand; a disulfide bond

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

Similar variants

ARSB p.Thr92Lys Pathogenic/Likely pathogenic ★★ same residue
ARSB p.Thr92Met Likely pathogenic ★★ same residue
SLURP1 p.Phe92Cys Uncertain significance ★ ⚠ same residue
ARSB p.Thr92= Likely benign ★ same residue
ARSB c.1142+1G>A Pathogenic ★★ same type
ARSB c.1142+1G>T Pathogenic ★★ same type
ARSB c.1142+2T>A Pathogenic/Likely pathogenic ★★ same type
ARSB c.1142+2T>C Pathogenic ★★ 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/arsb-p-thr92ala (accessed [today's date]).

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