Is WASHC5 p.Pro596= (c.1788C>G) pathogenic?

WASHC5 p.Pro596= (c.1788C>G) is classified Likely benign in WASHC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). Very rare (popmax 0.00167%, amr); Associated with hereditary spastic paraplegia 8.

What condition is associated with WASHC5 p.Pro596= (c.1788C>G)?

WASHC5 p.Pro596= (c.1788C>G) is associated with hereditary spastic paraplegia 8, Ritscher-Schinzel syndrome (ClinVar).

How common is WASHC5 p.Pro596= (c.1788C>G) in the general population?

WASHC5 p.Pro596= (c.1788C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Autosomal dominant spastic paraplegia type 8 inherited?

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

WASHC5 p.Pro596=

c.1788C>G · rs750716937 · VCV1979829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

hereditary spastic paraplegia 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.542	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.79, phastCons 1
Overall
CADD	9.801	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,526 alleles · very rare exomes 3/1,461,288 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
European (non-Finnish)	0.00017%	589,803

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: WASHC5
Protein: p.Pro596=
Coding: c.1788C>G
MANE Select: NM_014846
dbSNP: rs750716937
Type: single nucleotide variant
Location: chr8:125057643 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.27

Full WASHC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ritscher-Schinzel syndrome

For Autosomal dominant spastic paraplegia type 8 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

WASHC5 p.Gly696Asp Pathogenic/Likely pathogenic ★★ same condition
WASHC5 p.Gly696Ser Pathogenic/Likely pathogenic ★★ same condition
WASHC5 p.Leu619Phe Pathogenic ★★ same condition
WASHC5 p.Ser591Phe Pathogenic/Likely pathogenic ★★ same condition
WASHC5 p.Ser591Pro Pathogenic/Likely pathogenic ★★ same condition
WASHC5 p.Trp475Ter Pathogenic ★★ same condition
WASHC5 p.Val626Phe Pathogenic/Likely pathogenic ★★ same condition
WASHC5 c.2097+3A>G Uncertain significance ★★ 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/washc5-p-pro596 (accessed [today's date]).

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