Is DDHD1 p.Pro609fs (c.1824dup) pathogenic?

DDHD1 p.Pro609fs (c.1824dup) is classified Pathogenic in DDHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). Associated with hereditary spastic paraplegia 28.

What condition is associated with DDHD1 p.Pro609fs (c.1824dup)?

DDHD1 p.Pro609fs (c.1824dup) is associated with hereditary spastic paraplegia 28 (ClinVar).

How is Autosomal recessive spastic paraplegia type 28 inherited?

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

DDHD1 p.Pro609fs

c.1824dup · VCV3338263

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary spastic paraplegia 28

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 2, phastCons 1

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

Variant & gene context

Gene: DDHD1
Protein: p.Pro609fs
Coding: c.1824dup
MANE Select: NM_001160148
Type: Duplication
Location: chr14:53061143 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.11

Full DDHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 28 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 28 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

DDHD1 p.Gly133fs Pathogenic ★★ same condition
DDHD1 p.Ser108_Gly109dup Uncertain significance ★★ same condition
DDHD1 c.1993-19dup Benign/Likely benign ★★ same condition
DDHD1 p.Asn2fs Pathogenic ★ same condition
DDHD1 p.Leu115fs Pathogenic ★ same condition
DDHD1 p.Val349fs Pathogenic ★ same condition
DDHD1 p.Pro609Ser Uncertain significance ★ ⚠ same residue
DDHD1 c.1993-6dup Likely benign ★ 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/ddhd1-p-pro609fs (accessed [today's date]).

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