Is ARSI p.Arg97Leu (c.290G>T) pathogenic?

ARSI p.Arg97Leu (c.290G>T) is classified Uncertain significance in ARSI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely pathogenic (0.9783); Absent from gnomAD v4.1.

How common is ARSI p.Arg97Leu (c.290G>T) in the general population?

ARSI p.Arg97Leu (c.290G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSI p.Arg97Leu (c.290G>T)?

AlphaMissense predicts likely pathogenic (score 0.9783) — an in-silico prediction, not a clinical call.

ARSI p.Arg97Leu

c.290G>T · VCV3316618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9783 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,610)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9783	likely pathogenic · top 9% in ARSI
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -12.20	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 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 5,156 bp · p 0.021 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,596,610). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARSI
Protein: p.Arg97Leu
Coding: c.290G>T
MANE Select: NM_001012301
Type: single nucleotide variant
Location: chr5:150302084 (GRCh38)
Gene constraint: LOEUF 1.403 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.35

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

Similar variants

ARSI p.Arg97Trp Uncertain significance ★ ⚠ same residue
ARSI p.Ala216Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala259Val Uncertain significance ★★ ⚠ same type
ARSI p.Ala264Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala399Asp Uncertain significance ★★ ⚠ same type
ARSI p.Ala414Ser Uncertain significance ★★ ⚠ same type
ARSI p.Ala414Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala78Thr Uncertain significance ★★ ⚠ same type

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/arsi-p-arg97leu (accessed [today's date]).

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