Is ARSD p.Ser533Cys (c.1598C>G) pathogenic?

ARSD p.Ser533Cys (c.1598C>G) is classified Uncertain significance in ARSD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.1837); Absent from gnomAD v4.1.

How common is ARSD p.Ser533Cys (c.1598C>G) in the general population?

ARSD p.Ser533Cys (c.1598C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSD p.Ser533Cys (c.1598C>G)?

AlphaMissense predicts likely benign (score 0.1837) — an in-silico prediction, not a clinical call.

ARSD p.Ser533Cys

c.1598C>G · rs2519472884 · VCV2605118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1837	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -12.55	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.08	GERP -2.1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,698 bp · p 0.17 · regional, not allelic
Overall
CADD	16.72	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: ARSD
Protein: p.Ser533Cys
Coding: c.1598C>G
MANE Select: NM_001669
dbSNP: rs2519472884
Type: single nucleotide variant
Location: chrX:2907455 (GRCh38)
Structure: AlphaFold pLDDT 92.71

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

Similar variants

ARSD p.Cys577= Benign ★★ same type
ARSD p.Gly323= Likely benign ★★ same type
ARSD p.Gly409Glu Benign ★★ same type
ARSD p.Ser224Cys Benign ★★ ⚠ same type
ARSD p.Val500Ile Benign ★★ same type
ARSD p.Ala109Thr Uncertain significance ★ ⚠ same type
ARSD p.Ala14Thr Uncertain significance ★ ⚠ same type
ARSD p.Ala194Val 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/arsd-p-ser533cys (accessed [today's date]).

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