Is ARSJ p.Arg511Lys (c.1532G>A) pathogenic?

ARSJ p.Arg511Lys (c.1532G>A) is classified Uncertain significance in ARSJ (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.0668); Rare (popmax 0.163%, nfe).

How common is ARSJ p.Arg511Lys (c.1532G>A) in the general population?

ARSJ p.Arg511Lys (c.1532G>A) is rare (popmax 0.163%, nfe) (gnomAD).

What do computational predictors say about ARSJ p.Arg511Lys (c.1532G>A)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

ARSJ p.Arg511Lys

c.1532G>A · rs201324549 · VCV2352309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.163%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -5.44	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 2.1	GERP 0.66, phastCons 0.8
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.035 · regional, not allelic
Overall
CADD	17.06	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 0.163% European (non-Finnish) · 1,920/1,180,026 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.125% 2,021/1,613,970 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.163%	615
Finnishnot grpmax-eligible	0.0453%	2,207
Remaining individualsnot grpmax-eligible	0.0448%	2,232
African / African-American	0.0414%	2,416
Admixed American	0.0217%	4,615

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: ARSJ
Protein: p.Arg511Lys
Coding: c.1532G>A
MANE Select: NM_024590
dbSNP: rs201324549
Type: single nucleotide variant
Location: chr4:113902542 (GRCh38)
Gene constraint: LOEUF 0.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.34

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

Similar variants

ARSJ p.Arg511Trp Uncertain significance ★ ⚠ same residue
ARSJ p.Ala107Thr Uncertain significance ★ ⚠ same type
ARSJ p.Ala295Ser Uncertain significance ★ ⚠ same type
ARSJ p.Ala444Pro Uncertain significance ★ ⚠ same type
ARSJ p.Ala7Glu Uncertain significance ★ ⚠ same type
ARSJ p.Arg283Gln Uncertain significance ★ ⚠ same type
ARSJ p.Arg283Leu Uncertain significance ★ ⚠ same type
ARSJ p.Arg479Pro 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/arsj-p-arg511lys (accessed [today's date]).

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