Is SPG7 p.Pro760= (c.2280G>A) pathogenic?

SPG7 p.Pro760= (c.2280G>A) is classified Benign/Likely benign in SPG7 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-21). Low-frequency (popmax 2.05%, eas); Associated with hereditary spastic paraplegia.

What condition is associated with SPG7 p.Pro760= (c.2280G>A)?

SPG7 p.Pro760= (c.2280G>A) is associated with hereditary spastic paraplegia, hereditary spastic paraplegia 7 (ClinVar).

How common is SPG7 p.Pro760= (c.2280G>A) in the general population?

SPG7 p.Pro760= (c.2280G>A) is low-frequency (popmax 2.05%, eas) (gnomAD).

SPG7 p.Pro760=

c.2280G>A · rs11559075 · VCV139249

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.05%, eas)

Conditions

hereditary spastic paraplegia

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 -3.2	GERP -3.3
Overall
CADD	0.452	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.05% East Asian · 922/44,876 alleles

Filtering AF 1.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 1.3% 20,954/1,613,870 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.05%	49
Finnishnot grpmax-eligible	1.49%	67
European (non-Finnish)	1.41%	71
Remaining individualsnot grpmax-eligible	1.25%	80
Admixed American	1.02%	98
Ashkenazi Jewishnot grpmax-eligible	0.746%	134
South Asian	0.682%	147
Middle Eastern	0.547%	183
African / African-American	0.224%	447

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
Protein: p.Pro760=
Coding: c.2280G>A
MANE Select: NM_003119
dbSNP: rs11559075
Type: single nucleotide variant
Location: chr16:89556985 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.10 · 2 PDB
Residue 760: the 'disordered' region; the 'interaction with ppif' region

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

Disease context

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

Also linked: hereditary spastic paraplegia 7

Similar variants

SPG7 p.Pro760Leu Uncertain significance ★ ⚠ same residue
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

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-p-pro760 (accessed [today's date]).

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