Is ADSL p.Arg296Trp (c.886C>T) pathogenic?

ADSL p.Arg296Trp (c.886C>T) is classified Conflicting classifications of pathogenicity in ADSL (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.9243); Ultra-rare (popmax 0.0571%, sas); Associated with Inborn genetic diseases.

What condition is associated with ADSL p.Arg296Trp (c.886C>T)?

ADSL p.Arg296Trp (c.886C>T) is associated with Inborn genetic diseases, adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL p.Arg296Trp (c.886C>T) in the general population?

ADSL p.Arg296Trp (c.886C>T) is ultra-rare (popmax 0.0571%, sas) (gnomAD).

What do computational predictors say about ADSL p.Arg296Trp (c.886C>T)?

AlphaMissense predicts likely pathogenic (score 0.9243) — an in-silico prediction, not a clinical call.

ADSL p.Arg296Trp

c.886C>T · rs536254357 · VCV450065

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9243 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0571%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9243	likely pathogenic
REVEL	0.76	pathogenic-leaning
SaProt	LLR -15.63	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 20 kb · p 5.6e-07 · regional, not allelic
Overall
CADD	28.9	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

Grpmax group 0.0571% South Asian · 52/91,080 alleles

Filtering AF 0.0447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0403%

Overall 0.0109% 176/1,614,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0571%	1,752
European (non-Finnish)	0.01%	10,000
East Asian	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Admixed American	0.00167%	60,020
African / African-American	0.00133%	75,052

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: ADSL
Protein: p.Arg296Trp
Coding: c.886C>T
MANE Select: NM_000026
dbSNP: rs536254357
Type: single nucleotide variant
Location: chr22:40361511 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 4 PDB

Full ADSL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: adenylosuccinate lyase deficiency

Similar variants

ADSL p.Arg296Gln Uncertain significance ★★ ⚠ same residue
ADSL c.1191+5G>C Pathogenic/Likely pathogenic ★★ same condition
ADSL c.402+1G>T Likely pathogenic ★★ same condition
ADSL c.482+1G>C Likely pathogenic ★★ same condition
ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg141Trp Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg149Ter Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg190Gln 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/adsl-p-arg296trp (accessed [today's date]).

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