Is ARSJ p.Ala7Glu (c.20C>A) pathogenic?

ARSJ p.Ala7Glu (c.20C>A) is classified Uncertain significance in ARSJ (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.1045); Very rare (popmax 0.00505%, amr).

How common is ARSJ p.Ala7Glu (c.20C>A) in the general population?

ARSJ p.Ala7Glu (c.20C>A) is very rare (popmax 0.00505%, amr) (gnomAD).

What do computational predictors say about ARSJ p.Ala7Glu (c.20C>A)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

ARSJ p.Ala7Glu

c.20C>A · rs1727755143 · VCV2233573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00505%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -7.23	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 0.49	GERP -1.4
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.035 · regional, not allelic
Overall
CADD	13.52	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 0.00505% Admixed American · 3/59,368 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000672%

Overall 0.000343% 5/1,456,552 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00505%	19,789
East Asian	0.00446%	22,422

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.Ala7Glu
Coding: c.20C>A
MANE Select: NM_024590
dbSNP: rs1727755143
Type: single nucleotide variant
Location: chr4:113978815 (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.Ala107Thr Uncertain significance ★ ⚠ same type
ARSJ p.Ala295Ser Uncertain significance ★ ⚠ same type
ARSJ p.Ala444Pro 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
ARSJ p.Arg511Lys Uncertain significance ★ ⚠ same type
ARSJ p.Arg511Trp 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-ala7glu (accessed [today's date]).

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