Is ASL p.Ala240Val (c.719C>T) pathogenic?

ASL p.Ala240Val (c.719C>T) is classified Uncertain significance in ASL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely benign (0.1183); Very rare (popmax 0.00167%, amr); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Ala240Val (c.719C>T)?

ASL p.Ala240Val (c.719C>T) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Ala240Val (c.719C>T) in the general population?

ASL p.Ala240Val (c.719C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

What do computational predictors say about ASL p.Ala240Val (c.719C>T)?

AlphaMissense predicts likely benign (score 0.1183) — an in-silico prediction, not a clinical call.

ASL p.Ala240Val

c.719C>T · VCV4061749

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1183 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
AlphaMissense	0.1183	likely benign
REVEL	0.502	indeterminate
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.55, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic
Overall
CADD	17.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,828 alleles

Overall 0.000137% 2/1,459,608 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,828
European (non-Finnish)	8.48e-05%	1,178,860

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.Ala240Val
Coding: c.719C>T
MANE Select: NM_000048
Type: single nucleotide variant
Location: chr7:66088807 (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 240: 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.Ala240= Likely benign ★ 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
ASL c.446+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/asl-p-ala240val (accessed [today's date]).

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