Is PSAP p.Asp196= (c.588C>T) pathogenic?

PSAP p.Asp196= (c.588C>T) is classified Likely benign in PSAP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.134%, sas); Associated with Inborn genetic diseases.

What condition is associated with PSAP p.Asp196= (c.588C>T)?

PSAP p.Asp196= (c.588C>T) is associated with Inborn genetic diseases, metachromatic leukodystrophy due to saposin B deficiency, metachromatic leukodystrophy (ClinVar).

How common is PSAP p.Asp196= (c.588C>T) in the general population?

PSAP p.Asp196= (c.588C>T) is rare (popmax 0.134%, sas) (gnomAD).

PSAP p.Asp196=

c.588C>T · rs374869360 · VCV748199

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, sas)

Conditions

Inborn genetic diseases

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 -7.1	GERP -4
Overall
CADD	1.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% South Asian · 122/91,084 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.0126% 204/1,614,106 alleles · rare exomes 184/1,461,882 · genomes 20/152,224 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.134%	747
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
East Asian	0.00891%	11,222
European (non-Finnish)	0.00517%	19,345
African / African-American	0.004%	25,004
Finnishnot grpmax-eligible	0.00156%	64,008

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: PSAP
Protein: p.Asp196=
Coding: c.588C>T
MANE Select: NM_002778
dbSNP: rs374869360
Type: single nucleotide variant
Location: chr10:71828146 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 21 PDB
Residue 196: the saposin b-type 2 domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: metachromatic leukodystrophy due to saposin B deficiency metachromatic leukodystrophy

Similar variants

PSAP p.Asp196Asn Uncertain significance ★★ ⚠ same residue
PSAP p.Asp196Gly Uncertain significance ⚠ same residue
PSAP c.1005+1G>A Pathogenic/Likely pathogenic ★★ same condition
PSAP c.375+1G>T Likely pathogenic ★★ same condition
PSAP c.576+1G>A Likely pathogenic ★★ same condition
PSAP c.577-1G>T Pathogenic ★★ same condition
PSAP c.721-1G>A Likely pathogenic ★★ same condition
PSAP p.Asn215His 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/psap-p-asp196 (accessed [today's date]).

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