Is ARSG p.Cys522Arg (c.1564T>C) pathogenic?

ARSG p.Cys522Arg (c.1564T>C) is classified Uncertain significance in ARSG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: likely pathogenic (0.8996); Absent from gnomAD v4.1.

How common is ARSG p.Cys522Arg (c.1564T>C) in the general population?

ARSG p.Cys522Arg (c.1564T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSG p.Cys522Arg (c.1564T>C)?

AlphaMissense predicts likely pathogenic (score 0.8996) — an in-silico prediction, not a clinical call.

ARSG p.Cys522Arg

c.1564T>C · rs1388231577 · VCV1993632

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8996	likely pathogenic · top 10% in ARSG
REVEL	0.924	moderately pathogenic-leaning
SaProt	LLR -12.40	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 113 kb · p 0.075 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ARSG
Protein: p.Cys522Arg
Coding: c.1564T>C
MANE Select: NM_001267727
dbSNP: rs1388231577
Type: single nucleotide variant
Location: chr17:68420449 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90

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

Similar variants

ARSG c.1091+1G>A Likely pathogenic ★★ same type
ARSG c.982+2T>G Likely pathogenic ★★ same type
ARSG p.Ala180Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala262Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala313Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala374Pro Uncertain significance ★★ ⚠ same type
ARSG p.Ala437Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala473Val 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/arsg-p-cys522arg (accessed [today's date]).

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