Is ASNS p.Val96= (c.288G>A) pathogenic?

ASNS p.Val96= (c.288G>A) is classified Benign/Likely benign in ASNS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-15). Ultra-rare (popmax 0.0966%, sas); Associated with congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome.

How common is ASNS p.Val96= (c.288G>A) in the general population?

ASNS p.Val96= (c.288G>A) is ultra-rare (popmax 0.0966%, sas) (gnomAD).

ASNS p.Val96=

Q: What condition is associated with ASNS p.Val96= (c.288G>A)?

ASNS p.Val96= (c.288G>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.288G>A · rs554805942 · VCV1166409

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0966%, sas)

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 0.21	GERP -3.2, phastCons 0.97
Overall
CADD	10.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0966% South Asian · 88/91,076 alleles

Filtering AF 0.0803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0743%

Overall 0.00589% 95/1,613,898 alleles · ultra-rare exomes 84/1,461,586 · genomes 11/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0966%	1,035
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00133%	75,032

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.Val96=
Coding: c.288G>A
MANE Select: NM_001673
dbSNP: rs554805942
Type: single nucleotide variant
Location: chr7:97864458 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 96: the glutamine amidotransferase type-2 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 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
ASNS c.1476+2T>C Likely 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-val96 (accessed [today's date]).

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