Is ASL p.Ala26= (c.78G>A) pathogenic?

ASL p.Ala26= (c.78G>A) is classified Likely benign in ASL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-25). Ultra-rare (popmax 0.0165%, mid); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Ala26= (c.78G>A)?

ASL p.Ala26= (c.78G>A) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Ala26= (c.78G>A) in the general population?

ASL p.Ala26= (c.78G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Ala26=

c.78G>A · rs115069006 · VCV1078755

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

argininosuccinic aciduria

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 -11	GERP -3
Overall
CADD	0.219	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0018% 29/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00669%	14,957
South Asian	0.0022%	45,541
European (non-Finnish)	0.00178%	56,192
Admixed American	0.00167%	59,994
African / African-American	0.00133%	75,052

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: ASL
Protein: p.Ala26=
Coding: c.78G>A
MANE Select: NM_000048
dbSNP: rs115069006
Type: single nucleotide variant
Location: chr7:66081868 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB

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

Disease context

argininosuccinic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Argininosuccinic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

ASL p.Ala26Thr Uncertain significance ★★ ⚠ same residue
ASL p.Ala26Val Uncertain significance ★ ⚠ same residue
ASL c.1062+5G>C Likely pathogenic ★★ same condition
ASL c.1143+1G>T Pathogenic/Likely pathogenic ★★ same condition
ASL c.13-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASL c.291+1G>T Likely pathogenic ★★ same condition
ASL c.348+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASL c.349-1G>A 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/asl-p-ala26 (accessed [today's date]).

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