Is WASHC5 p.Pro244= (c.732G>A) pathogenic?

WASHC5 p.Pro244= (c.732G>A) is classified Benign/Likely benign in WASHC5 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0864%, nfe); Associated with hereditary spastic paraplegia 8.

What condition is associated with WASHC5 p.Pro244= (c.732G>A)?

WASHC5 p.Pro244= (c.732G>A) is associated with hereditary spastic paraplegia 8, hereditary spastic paraplegia, Ritscher-Schinzel syndrome (ClinVar).

How common is WASHC5 p.Pro244= (c.732G>A) in the general population?

WASHC5 p.Pro244= (c.732G>A) is ultra-rare (popmax 0.0864%, nfe) (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.Pro244=

c.732G>A · rs146320386 · VCV361729

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0864%, nfe)

Conditions

hereditary spastic paraplegia 8

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 -15	GERP -4
Overall
CADD	1.204	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0864% European (non-Finnish) · 1,020/1,179,958 alleles

Filtering AF 0.082% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0802%

Overall 0.0967% 1,561/1,613,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.683%	146
Remaining individualsnot grpmax-eligible	0.122%	822
European (non-Finnish)grpmax	0.0864%	1,157
Admixed American	0.0333%	2,999
Middle Eastern	0.0165%	6,062
East Asian	0.00446%	22,439
South Asian	0.00329%	30,357
African / African-American	0.00267%	37,472

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro244=
Coding: c.732G>A
MANE Select: NM_014846
dbSNP: rs146320386
Type: single nucleotide variant
Location: chr8:125076480 (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: hereditary spastic paraplegia 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-pro244 (accessed [today's date]).

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