Is SETX p.Pro2571Ser (c.7711C>T) pathogenic?

SETX p.Pro2571Ser (c.7711C>T) is classified Uncertain significance in SETX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-04-26). AlphaMissense: likely benign (0.0884); Very rare (popmax 0.0011%, sas); Associated with proximal spinal muscular atrophy.

What condition is associated with SETX p.Pro2571Ser (c.7711C>T)?

SETX p.Pro2571Ser (c.7711C>T) is associated with proximal spinal muscular atrophy (ClinVar).

How common is SETX p.Pro2571Ser (c.7711C>T) in the general population?

SETX p.Pro2571Ser (c.7711C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Proximal spinal muscular atrophy inherited?

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

What do computational predictors say about SETX p.Pro2571Ser (c.7711C>T)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

SETX p.Pro2571Ser

c.7711C>T · rs1554801479 · VCV549704

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

proximal spinal muscular atrophy

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 671 bp · p 0.36 · regional, not allelic
Overall
CADD	16.1	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

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,120 alleles · very rare exomes 6/1,461,778 · genomes 0/152,342 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	0.000424%	236,005

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.Pro2571Ser
Coding: c.7711C>T
MANE Select: NM_015046
dbSNP: rs1554801479
Type: single nucleotide variant
Location: chr9:132264562 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.93
Residue 2571: the 'disordered' region

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

Disease context

proximal spinal muscular atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Proximal spinal muscular atrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

SETX p.Pro2571Arg Uncertain significance ★ ⚠ same residue
SETX p.Pro2571= Likely benign ★ same residue
SETX p.Pro2571del Uncertain significance ★★ same residue
SETX p.Arg111Ter Pathogenic ★★ same type
SETX p.Arg1363Ter Pathogenic ★★ same type
SETX p.Arg1606Ter Pathogenic ★★ same type
SETX p.Arg1778Ter Pathogenic/Likely pathogenic ★★ same type
SETX p.Arg2098Ter Pathogenic ★★ 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/setx-p-pro2571ser (accessed [today's date]).

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