Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 95.7%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
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 3.5 | GERP 0.47, phastCons 1 |
| Overall | ||
| CADD | 13.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
95.7%
East Asian · 42,789/44,704 alleles
Filtering AF
95%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 94.6%
Overall
82.4%
1,327,840/1,611,876 alleles · common
exomes 1,216,508/1,460,090 · genomes 111,332/151,786 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 95.7% | 1 |
| Finnishnot grpmax-eligible | 88.9% | 1 |
| South Asian | 88.1% | 1 |
| Admixed American | 85.9% | 1 |
| Amishnot grpmax-eligible | 84.6% | 1 |
| European (non-Finnish) | 83.6% | 1 |
| Remaining individualsnot grpmax-eligible | 81.3% | 1 |
| Middle Eastern | 80.4% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 78.9% | 1 |
| African / African-American | 42.7% | 2 |
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.Phe91=
- Coding
- c.273C>T
- MANE Select
- NM_001160148
- dbSNP
- rs2358189
- Type
- single nucleotide variant
- Location
- chr14:53152826 (GRCh38)
- Gene constraint
- LOEUF 0.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 67.11
Disease context
hereditary spastic paraplegia 28 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Autosomal recessive spastic paraplegia type 28 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Childhood, Infancy
Similar variants
- 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
- DDHD1 p.Arg596Gln 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-phe91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown