Is SETX p.Ser985= (c.2955G>A) pathogenic?

SETX p.Ser985= (c.2955G>A) is classified Benign/Likely benign in SETX (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0307%, afr); Associated with spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2.

How common is SETX p.Ser985= (c.2955G>A) in the general population?

SETX p.Ser985= (c.2955G>A) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

SETX p.Ser985=

Q: What condition is associated with SETX p.Ser985= (c.2955G>A)?

SETX p.Ser985= (c.2955G>A) is associated with spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, amyotrophic lateral sclerosis type 4 (ClinVar).

Q: How is Spinocerebellar ataxia with axonal neuropathy type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2955G>A · rs201251074 · VCV767351

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Conditions

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.064	GERP -2.3
Overall
CADD	7.904	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,956 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.0113% 183/1,612,952 alleles · ultra-rare exomes 137/1,460,748 · genomes 46/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,259
Finnishnot grpmax-eligible	0.0203%	4,915
European (non-Finnish)	0.0114%	8,737
Remaining individualsnot grpmax-eligible	0.0112%	8,920
Admixed American	0.00334%	29,931
South Asian	0.0033%	30,305

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: SETX
Protein: p.Ser985=
Coding: c.2955G>A
MANE Select: NM_015046
dbSNP: rs201251074
Type: single nucleotide variant
Location: chr9:132328643 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.93

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

Disease context

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 4

For Spinocerebellar ataxia with axonal neuropathy type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (France)

Similar variants

SETX p.Ser985Leu Likely benign ★★ same residue
SETX p.Arg111Ter Pathogenic ★★ same condition
SETX p.Arg1363Ter Pathogenic ★★ same condition
SETX p.Arg1606Ter Pathogenic ★★ same condition
SETX p.Arg1778Ter Pathogenic/Likely pathogenic ★★ same condition
SETX p.Arg2098Ter Pathogenic ★★ same condition
SETX p.Arg332Trp Pathogenic/Likely pathogenic ★★ same condition
SETX p.Arg778Ter 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/setx-p-ser985 (accessed [today's date]).

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