Is PSAP p.Lys262fs (c.785_788del) pathogenic?

PSAP p.Lys262fs (c.785788del) is classified Pathogenic in PSAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). No gnomAD frequency available for this variant; Associated with metachromatic leukodystrophy due to saposin B deficiency.

What condition is associated with PSAP p.Lys262fs (c.785_788del)?

PSAP p.Lys262fs (c.785_788del) is associated with metachromatic leukodystrophy due to saposin B deficiency (ClinVar).

How common is PSAP p.Lys262fs (c.785_788del) in the general population?

PSAP p.Lys262fs (c.785_788del) is no gnomAD frequency available for this variant (gnomAD).

How is Metachromatic leukodystrophy inherited?

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

PSAP p.Lys262fs

c.785_788del · rs2494506149 · VCV2694009

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

metachromatic leukodystrophy due to saposin B deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 8 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.77	GERP -2.1, phastCons 0.005

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PSAP
Protein: p.Lys262fs
Coding: c.785_788del
MANE Select: NM_002778
dbSNP: rs2494506149
Type: Deletion
Location: chr10:71821997 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 21 PDB
Residue 262: the saposin b-type 2 domain; a disulfide bond; an α-helix

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

Disease context

metachromatic leukodystrophy due to saposin B deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Metachromatic leukodystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

PSAP p.Lys262Glu Uncertain significance ★ ⚠ same residue
PSAP p.Lys262= Likely benign ★ same residue
PSAP c.720+2_720+5del Likely pathogenic ★★ same condition
PSAP p.Lys227del Pathogenic/Likely pathogenic ★★ same condition
PSAP c.41-17_42del Likely pathogenic ★ same condition
PSAP p.Asp272fs Pathogenic ★ same condition
PSAP p.Asp68fs Pathogenic ★ same condition
PSAP p.Gln203fs 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/psap-p-lys262fs (accessed [today's date]).

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