DDHD2 p.Phe441=
c.1323C>T · rs1183950102 · VCV750435
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.49e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.34 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.38 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP -4.5, phastCons 0.98 |
| Overall | ||
| CADD | 9.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.49e-05%
European (non-Finnish) · 1/1,177,480 alleles
Overall
6.86e-05%
1/1,458,400 alleles · very rare
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.Phe441=
- Coding
- c.1323C>T
- MANE Select
- NM_015214
- dbSNP
- rs1183950102
- Type
- single nucleotide variant
- Location
- chr8:38249782 (GRCh38)
- Gene constraint
- LOEUF 0.758 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.70
- Residue 441
- a UniProt-annotated variant site (in spg54; likely pathogenic; loss of triacylglycerol hydrolase activity); the sam domain
Similar variants
- DDHD2 c.1126-2A>G Likely pathogenic ★★ same type
- DDHD2 c.1248+2T>C Likely pathogenic ★★ same type
- DDHD2 p.Arg232Ter Pathogenic ★★ same type
- DDHD2 p.Arg329Ter Pathogenic ★★ same type
- DDHD2 p.Arg422Ter Likely pathogenic ★★ same type
- DDHD2 p.Arg516Ter Pathogenic ★★ same type
- DDHD2 p.Asp660His Pathogenic/Likely pathogenic ★★ same type
- DDHD2 p.Gln286Ter Pathogenic/Likely pathogenic ★★ same type
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-phe441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown