Is ASL p.Arg306Trp (c.916C>T) pathogenic?

ASL p.Arg306Trp (c.916C>T) is classified Conflicting classifications of pathogenicity in ASL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-19). AlphaMissense: likely benign (0.2756); Absent from gnomAD v4.1; Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Arg306Trp (c.916C>T)?

ASL p.Arg306Trp (c.916C>T) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Arg306Trp (c.916C>T) in the general population?

ASL p.Arg306Trp (c.916C>T) is absent from gnomAD v4.1 (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.Arg306Trp (c.916C>T)?

AlphaMissense predicts likely benign (score 0.2756) — an in-silico prediction, not a clinical call.

ASL p.Arg306Trp

c.916C>T · rs868834862 · VCV553483

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2756 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
AlphaMissense	0.2756	likely benign
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -11.16	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.90	donor gain · deltas
Pangolin	Δ0.71	gain · loss 0.64 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.1	GERP 1.4, phastCons 0.96
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASL
Protein: p.Arg306Trp
Coding: c.916C>T
MANE Select: NM_000048
dbSNP: rs868834862
Type: single nucleotide variant
Location: chr7:66089173 (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 306: an α-helix; a UniProt-annotated variant site (in arginsa; severe)

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.Arg306Pro Uncertain significance ★ ⚠ same residue
ASL p.Arg306= 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

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-arg306trp (accessed [today's date]).

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