Is ARSB p.Pro244Thr (c.730C>A) pathogenic?

ARSB p.Pro244Thr (c.730C>A) is classified Likely pathogenic in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-17). AlphaMissense: likely pathogenic (0.639); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARSB p.Pro244Thr (c.730C>A)?

ARSB p.Pro244Thr (c.730C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARSB p.Pro244Thr (c.730C>A) in the general population?

ARSB p.Pro244Thr (c.730C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSB p.Pro244Thr (c.730C>A)?

AlphaMissense predicts likely pathogenic (score 0.639) — an in-silico prediction, not a clinical call.

ARSB p.Pro244Thr

c.730C>A · rs1751681202 · VCV985675

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.639 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.639	likely pathogenic ✓ concordant with ClinVar
REVEL	0.981	strongly pathogenic-leaning
SaProt	LLR -13.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	28.4	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: ARSB
Protein: p.Pro244Thr
Coding: c.730C>A
MANE Select: NM_000046
dbSNP: rs1751681202
Type: single nucleotide variant
Location: chr5:78955463 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 244: a disulfide bond; a β-strand

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.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
ARSB p.Pro228Leu 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-pro244thr (accessed [today's date]).

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