DDHD2 p.Arg516Ter
c.1546C>T · rs373856119 · VCV39680
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -0.45, phastCons 0.98 |
| Overall | ||
| CADD | 36.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.00781% | 12,804 |
| East Asiangrpmax | 0.00223% | 44,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| African / African-American | 0.00134% | 74,888 |
| European (non-Finnish) | 0.00102% | 98,334 |
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
- DDHD2
- Protein
- p.Arg516Ter
- Coding
- c.1546C>T
- MANE Select
- NM_015214
- dbSNP
- rs373856119
- Type
- single nucleotide variant
- Location
- chr8:38252216 (GRCh38)
- Gene constraint
- LOEUF 0.758 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.70
- Residue 516
- a UniProt-annotated variant site (in spg54; likely pathogenic; loss of triacylglycerol hydrolase activity); the ddhd domain
Disease context
hereditary spastic paraplegia 54 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Autosomal recessive spastic paraplegia type 54 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy
Similar variants
- DDHD2 p.Arg516Gln Uncertain significance ★★ ⚠ same residue
- 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
- DDHD2 p.Asp660His Pathogenic/Likely pathogenic ★★ same condition
- DDHD2 p.Gln286Ter Pathogenic/Likely pathogenic ★★ same condition
- DDHD2 p.Trp115Ter 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-arg516ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown