Is DDHD1 p.Pro151= (c.453G>A) pathogenic?

DDHD1 p.Pro151= (c.453G>A) is classified Benign in DDHD1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 8.42%, amr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spastic paraplegia 28.

What condition is associated with DDHD1 p.Pro151= (c.453G>A)?

DDHD1 p.Pro151= (c.453G>A) is associated with hereditary spastic paraplegia 28, hereditary spastic paraplegia (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.Pro151=

Q: How common is DDHD1 p.Pro151= (c.453G>A) in the general population?

DDHD1 p.Pro151= (c.453G>A) is common (popmax 8.42%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.453G>A · rs141323589 · VCV380446

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 8.42%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary spastic paraplegia 28

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 -3.8	GERP -0.52
Overall
CADD	4.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.42% Admixed American · 5,049/59,992 alleles

Filtering AF 8.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.14%

Overall 0.351% 5,660/1,613,068 alleles · common exomes 4,673/1,460,760 · genomes 987/152,308 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	8.42%	12
East Asian	0.399%	251
Remaining individualsnot grpmax-eligible	0.351%	285
Ashkenazi Jewishnot grpmax-eligible	0.135%	740
African / African-American	0.125%	798
Middle Eastern	0.0165%	6,062
South Asian	0.0154%	6,506
European (non-Finnish)	0.00525%	19,030
Finnishnot grpmax-eligible	0.00316%	31,610

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: DDHD1
Protein: p.Pro151=
Coding: c.453G>A
MANE Select: NM_001160148
dbSNP: rs141323589
Type: single nucleotide variant
Location: chr14:53152646 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.11
Residue 151: the 'disordered' region

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

Also linked: hereditary spastic paraplegia

For Autosomal recessive spastic paraplegia type 28 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

DDHD1 p.Pro151Leu Uncertain significance ★ ⚠ same residue
DDHD1 p.Ala193Val Uncertain significance ★★ ⚠ same condition
DDHD1 p.Ala94Pro Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg204Trp Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg288His Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg554Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg570Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg588Gln 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/ddhd1-p-pro151 (accessed [today's date]).

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