Is SPG7 c.1663+5A>G pathogenic?

SPG7 c.1663+5A>G is classified Uncertain significance in SPG7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). Very rare (popmax 0.0011%, sas); Associated with hereditary spastic paraplegia 7.

What condition is associated with SPG7 c.1663+5A>G?

SPG7 c.1663+5A>G is associated with hereditary spastic paraplegia 7 (ClinVar).

How common is SPG7 c.1663+5A>G in the general population?

SPG7 c.1663+5A>G is very rare (popmax 0.0011%, sas) (gnomAD).

How is Spastic paraplegia type 7 inherited?

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

SPG7 c.1663+5A>G

VCV4749180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary spastic paraplegia 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP -3.4, phastCons 0.36
Overall
CADD	11.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,894 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000376% 6/1,593,760 alleles · very rare exomes 6/1,441,396 · genomes 0/152,364 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,894
European (non-Finnish)	0.000427%	234,195

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: SPG7
Coding: c.1663+5A>G
MANE Select: NM_003119
Type: single nucleotide variant
Location: chr16:89548118 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.10 · 2 PDB

Full SPG7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spastic paraplegia type 7 (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

SPG7 c.1324+2T>G Pathogenic/Likely pathogenic ★★ same condition
SPG7 c.1552+1G>T Pathogenic/Likely pathogenic ★★ same condition
SPG7 c.1553-2A>G Pathogenic/Likely pathogenic ★★ same condition
SPG7 c.1779+1G>T Pathogenic/Likely pathogenic ★★ same condition
SPG7 c.1936+2T>A Likely pathogenic ★★ same condition
SPG7 c.1937-2A>G Pathogenic ★★ same condition
SPG7 c.2104-2A>G Pathogenic/Likely pathogenic ★★ same condition
SPG7 c.286+1G>T 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/spg7-c-1663-plus-5a-g (accessed [today's date]).

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