Is ASL p.Arg186= (c.556C>A) pathogenic?

ASL p.Arg186= (c.556C>A) is classified Benign/Likely benign in ASL (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.31%, afr); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Arg186= (c.556C>A)?

ASL p.Arg186= (c.556C>A) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Arg186= (c.556C>A) in the general population?

ASL p.Arg186= (c.556C>A) is low-frequency (popmax 1.31%, afr) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Arg186=

c.556C>A · rs111407265 · VCV136422

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, afr)

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 1.3	GERP -3.1, phastCons 1
Overall
CADD	8.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.31% African / African-American · 978/74,834 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.21%

Overall 0.0888% 1,421/1,599,348 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.31%	77
Middle Eastern	0.298%	336
Admixed American	0.246%	407
Remaining individualsnot grpmax-eligible	0.184%	543
European (non-Finnish)	0.0144%	6,944
South Asian	0.00112%	89,362

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.Arg186=
Coding: c.556C>A
MANE Select: NM_000048
dbSNP: rs111407265
Type: single nucleotide variant
Location: chr7:66086775 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB
Residue 186: a UniProt-annotated variant site (in arginsa; reduction of argininosuccinate lyase activity; reduces protein expression); an α-helix

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.Arg186Gln Pathogenic ★★ ⚠ same residue
ASL p.Arg186Trp Pathogenic/Likely pathogenic ★★ ⚠ same residue
ASL p.Arg186_Leu187insGlyThrAspProArgLeuTer Pathogenic ★★ 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

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-arg186 (accessed [today's date]).

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