Is ASS1 p.Arg100Leu (c.299G>T) pathogenic?

ASS1 p.Arg100Leu (c.299G>T) is classified Uncertain significance in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely benign (0.28); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASS1 p.Arg100Leu (c.299G>T)?

ASS1 p.Arg100Leu (c.299G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASS1 p.Arg100Leu (c.299G>T) in the general population?

ASS1 p.Arg100Leu (c.299G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASS1 p.Arg100Leu (c.299G>T)?

AlphaMissense predicts likely benign (score 0.28) — an in-silico prediction, not a clinical call.

ASS1 p.Arg100Leu

c.299G>T · rs138279074 · VCV2264953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.28 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.28	likely benign
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -6.64	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 0.29, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	27.3	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: ASS1
Protein: p.Arg100Leu
Coding: c.299G>T
MANE Select: NM_054012
dbSNP: rs138279074
Type: single nucleotide variant
Location: chr9:130458525 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 100: an α-helix; a UniProt-annotated variant site (in ctln1)

Full ASS1 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

Similar variants

ASS1 p.Arg100His Uncertain significance ★★ ⚠ same residue
ASS1 p.Arg100Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ASS1 p.Arg100= Likely benign ★ same residue
ASS1 p.Arg153Gln Uncertain significance ★★ ⚠ same condition
ASS1 p.Gly5Ala Uncertain significance ★★ ⚠ same condition
ASS1 p.Pro178Leu Uncertain significance ★★ ⚠ same condition
ASS1 p.Pro385Ala Uncertain significance ★★ ⚠ same condition
ASS1 p.Thr219Asn Uncertain significance ★★ ⚠ 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/ass1-p-arg100leu (accessed [today's date]).

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