Is AP5Z1 p.Ser385= (c.1155G>A) pathogenic?

AP5Z1 p.Ser385= (c.1155G>A) is classified Benign/Likely benign in AP5Z1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-18). Rare (popmax 0.314%, afr); Associated with hereditary spastic paraplegia 48.

What condition is associated with AP5Z1 p.Ser385= (c.1155G>A)?

AP5Z1 p.Ser385= (c.1155G>A) is associated with hereditary spastic paraplegia 48, hereditary spastic paraplegia (ClinVar).

How common is AP5Z1 p.Ser385= (c.1155G>A) in the general population?

AP5Z1 p.Ser385= (c.1155G>A) is rare (popmax 0.314%, afr) (gnomAD).

How is Autosomal recessive spastic paraplegia type 48 inherited?

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

AP5Z1 p.Ser385=

c.1155G>A · rs370926189 · VCV696635

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.314%, afr)

Conditions

hereditary spastic paraplegia 48

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 -11	GERP -3.1
Overall
CADD	0.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.314% African / African-American · 235/74,950 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.268%

Overall 0.0544% 876/1,610,320 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.314%	319
Middle Eastern	0.0996%	1,004
Remaining individualsnot grpmax-eligible	0.0866%	1,155
Admixed American	0.0668%	1,496
European (non-Finnish)	0.0456%	2,193
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,404
South Asian	0.0022%	45,432
Finnishnot grpmax-eligible	0.00157%	63,560

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: AP5Z1
Protein: p.Ser385=
Coding: c.1155G>A
MANE Select: NM_014855
dbSNP: rs370926189
Type: single nucleotide variant
Location: chr7:4786272 (GRCh38)
Gene constraint: LOEUF 1.641 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.32

Full AP5Z1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 48 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia

For Autosomal recessive spastic paraplegia type 48 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

AP5Z1 p.Ser385Leu Uncertain significance ★ ⚠ same residue
AP5Z1 c.1312-2A>G Pathogenic/Likely pathogenic ★★ same condition
AP5Z1 c.1707+1G>A Likely pathogenic ★★ same condition
AP5Z1 c.1806-1G>C Likely pathogenic ★★ same condition
AP5Z1 p.Arg138Ter Pathogenic/Likely pathogenic ★★ same condition
AP5Z1 p.Arg310Ter Pathogenic/Likely pathogenic ★★ same condition
AP5Z1 p.Arg311Ter Pathogenic/Likely pathogenic ★★ same condition
AP5Z1 p.Arg345Ter 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/ap5z1-p-ser385 (accessed [today's date]).

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