Is ASL p.Val448= (c.1344C>T) pathogenic?

ASL p.Val448= (c.1344C>T) is classified Likely benign in ASL (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-17). Very rare (popmax 0.00667%, afr); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Val448= (c.1344C>T)?

ASL p.Val448= (c.1344C>T) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Val448= (c.1344C>T) in the general population?

ASL p.Val448= (c.1344C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Val448=

c.1344C>T · rs144011206 · VCV794983

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, 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 -5.1	GERP -0.95
Overall
CADD	2.693	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,936 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000992% 16/1,612,572 alleles · very rare exomes 14/1,460,354 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,987
South Asian	0.00329%	30,361
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	0.000508%	196,661

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.Val448=
Coding: c.1344C>T
MANE Select: NM_000048
dbSNP: rs144011206
Type: single nucleotide variant
Location: chr7:66092861 (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 448: 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.Val448Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val448 (accessed [today's date]).

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