Is SETX p.Ser2598Arg (c.7794C>A) pathogenic?

SETX p.Ser2598Arg (c.7794C>A) is classified Uncertain significance in SETX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-17). AlphaMissense: likely benign (0.2453); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SETX p.Ser2598Arg (c.7794C>A)?

SETX p.Ser2598Arg (c.7794C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SETX p.Ser2598Arg (c.7794C>A) in the general population?

SETX p.Ser2598Arg (c.7794C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETX p.Ser2598Arg (c.7794C>A)?

AlphaMissense predicts likely benign (score 0.2453) — an in-silico prediction, not a clinical call.

SETX p.Ser2598Arg

c.7794C>A · rs2538819417 · VCV1760649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2453 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2453	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.2	GERP -0.25, phastCons 0.89
Regional constraint	o/e 1.05	unconstrained · MANE · 671 bp · p 0.36 · regional, not allelic
Overall
CADD	15.82	PHRED · no single calibrated threshold — expert panels disagree

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

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: SETX
Protein: p.Ser2598Arg
Coding: c.7794C>A
MANE Select: NM_015046
dbSNP: rs2538819417
Type: single nucleotide variant
Location: chr9:132264479 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.93
Residue 2598: the 'disordered' region

Full SETX 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

SETX p.Arg1363Ter Pathogenic ★★ same condition
SETX p.Ala1945Val Uncertain significance ★★ ⚠ same condition
SETX p.Ala2596Pro Uncertain significance ★★ ⚠ same condition
SETX p.Ala488Thr Uncertain significance ★★ ⚠ same condition
SETX p.Arg1214Ser Uncertain significance ★★ ⚠ same condition
SETX p.Arg1302Leu Uncertain significance ★★ same condition
SETX p.Arg1846His Uncertain significance ★★ ⚠ same condition
SETX p.Arg1846Leu 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/setx-p-ser2598arg (accessed [today's date]).

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