Is ASNS p.Arg529= (c.1587G>A) pathogenic?

ASNS p.Arg529= (c.1587G>A) is classified Benign/Likely benign in ASNS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.669%, afr); Associated with congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome.

How common is ASNS p.Arg529= (c.1587G>A) in the general population?

ASNS p.Arg529= (c.1587G>A) is rare (popmax 0.669%, afr) (gnomAD).

ASNS p.Arg529=

Q: What condition is associated with ASNS p.Arg529= (c.1587G>A)?

ASNS p.Arg529= (c.1587G>A) is associated with congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome (ClinVar).

Q: How is Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1587G>A · rs140975053 · VCV728953

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.669%, afr)

Conditions

congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -0.17, phastCons 0.24
Overall
CADD	7.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.669% African / African-American · 502/75,032 alleles

Filtering AF 0.621% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.601%

Overall 0.0339% 548/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.669%	149
Middle Eastern	0.0495%	2,020
Admixed American	0.0333%	2,999
Remaining individualsnot grpmax-eligible	0.032%	3,126
European (non-Finnish)	0.000254%	393,345

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: ASNS
Protein: p.Arg529=
Coding: c.1587G>A
MANE Select: NM_001673
dbSNP: rs140975053
Type: single nucleotide variant
Location: chr7:97852358 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 529: the asparagine synthetase domain

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

Disease context

congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ASNS p.Arg529Gln Uncertain significance ★ ⚠ same residue
ASNS c.1030+1G>A Likely pathogenic ★★ same condition
ASNS c.1138-1G>A Likely pathogenic ★★ same condition
ASNS c.1239-2A>T Likely pathogenic ★★ same condition
ASNS c.1320+1G>C Likely pathogenic ★★ same condition
ASNS c.1320+1G>T Likely pathogenic ★★ same condition
ASNS c.1321-1G>A Likely pathogenic ★★ same condition
ASNS c.1476+1G>A Pathogenic ★★ 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/asns-p-arg529 (accessed [today's date]).

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