DDHD2 p.Tyr492=
c.1476C>T · rs755434256 · VCV701780
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0735%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1 | GERP -4.5, phastCons 0.001 |
| Overall | ||
| CADD | 3.347 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0735%
East Asian · 33/44,890 alleles
Filtering AF
0.0537%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.047%
Overall
0.00235%
38/1,613,768 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0735% | 1,360 |
| African / African-American | 0.00267% | 37,439 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 0.00017% | 589,967 |
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.Tyr492=
- Coding
- c.1476C>T
- MANE Select
- NM_015214
- dbSNP
- rs755434256
- Type
- single nucleotide variant
- Location
- chr8:38252146 (GRCh38)
- Gene constraint
- LOEUF 0.758 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.70
- Residue 492
- a UniProt-annotated variant site (in spg54; likely pathogenic; loss of triacylglycerol hydrolase activity)
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-tyr492 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown