Is ASNS p.Ala6= (c.18G>A) pathogenic?

ASNS p.Ala6= (c.18G>A) is classified Benign in ASNS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.63%, afr); Associated with congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome.

How common is ASNS p.Ala6= (c.18G>A) in the general population?

ASNS p.Ala6= (c.18G>A) is low-frequency (popmax 2.63%, afr) (gnomAD).

ASNS p.Ala6=

Q: What condition is associated with ASNS p.Ala6= (c.18G>A)?

ASNS p.Ala6= (c.18G>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.18G>A · rs76996735 · VCV771726

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.63%, 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 -0.17	GERP -1.1, phastCons 0.054
Overall
CADD	13.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.63% African / African-American · 1,971/75,028 alleles

Filtering AF 2.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.49%

Overall 0.366% 5,909/1,613,962 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.63%	38
South Asian	1.22%	82
East Asian	1.01%	99
Middle Eastern	0.957%	105
Admixed American	0.865%	116
Remaining individualsnot grpmax-eligible	0.578%	173
European (non-Finnish)	0.122%	822
Finnishnot grpmax-eligible	0.00312%	32,017

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.Ala6=
Coding: c.18G>A
MANE Select: NM_001673
dbSNP: rs76996735
Type: single nucleotide variant
Location: chr7:97869139 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 6: a UniProt-annotated variant site (in asnsd; dramatic reduction in protein abundance); the glutamine amidotransferase type-2 domain; a β-strand

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.Ala6Val 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-ala6 (accessed [today's date]).

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