Is ASL p.Ala177= (c.531C>T) pathogenic?

ASL p.Ala177= (c.531C>T) is classified Likely benign in ASL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-08). Very rare (popmax 0.00512%, amr); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Ala177= (c.531C>T)?

ASL p.Ala177= (c.531C>T) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Ala177= (c.531C>T) in the general population?

ASL p.Ala177= (c.531C>T) is very rare (popmax 0.00512%, amr) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Ala177=

c.531C>T · rs201974677 · VCV1139934

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00512%, amr)

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 -14	GERP -3.1
Overall
CADD	0.251	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00512% Admixed American · 3/58,610 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00226%

Overall 0.0028% 45/1,605,752 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00512%	19,537
European (non-Finnish)	0.0034%	29,420
East Asian	0.00224%	44,556
African / African-American	0.00134%	74,796

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.Ala177=
Coding: c.531C>T
MANE Select: NM_000048
dbSNP: rs201974677
Type: single nucleotide variant
Location: chr7:66086750 (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 177: 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.Ala177Gly Uncertain significance ★★ ⚠ same residue
ASL p.Ala177_Val178insAla 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-ala177 (accessed [today's date]).

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