Is DDHD2 p.His273fs (c.819_820del) pathogenic?

DDHD2 p.His273fs (c.819820del) is classified Pathogenic in DDHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). Absent from gnomAD; Associated with hereditary spastic paraplegia 54.

What condition is associated with DDHD2 p.His273fs (c.819_820del)?

DDHD2 p.His273fs (c.819_820del) is associated with hereditary spastic paraplegia 54 (ClinVar).

How common is DDHD2 p.His273fs (c.819_820del) in the general population?

DDHD2 p.His273fs (c.819_820del) is absent from gnomAD (gnomAD).

How is Autosomal recessive spastic paraplegia type 54 inherited?

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

DDHD2 p.His273fs

c.819_820del · rs2486857105 · VCV3068415

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

hereditary spastic paraplegia 54

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 7 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 0.92, phastCons 1

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: DDHD2
Protein: p.His273fs
Coding: c.819_820del
MANE Select: NM_015214
dbSNP: rs2486857105
Type: Microsatellite
Location: chr8:38242354 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.70

Full DDHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 54 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 54 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

DDHD2 p.Glu644del Uncertain significance ★ same condition
DDHD2 p.Ile162del Uncertain significance ★ same condition
DDHD2 c.1058-16_1058-14del Likely benign ★ same condition
DDHD2 c.2054+10_2054+12del Likely benign ★ same condition
DDHD2 c.1126-2A>G Likely pathogenic ★★ same condition
DDHD2 c.1248+2T>C Likely pathogenic ★★ same condition
DDHD2 p.Arg232Ter Pathogenic ★★ same condition
DDHD2 p.Arg329Ter 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/ddhd2-p-his273fs (accessed [today's date]).

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