SEC24D p.Ala905=
c.2715C>T · rs762216451 · VCV794453
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0357%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -3.6 |
| Overall | ||
| CADD | 6.712 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0357%
East Asian · 16/44,880 alleles
Filtering AF
0.0223%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0182%
Overall
0.00143%
23/1,614,000 alleles · ultra-rare
exomes 21/1,461,828 · genomes 2/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0357% | 2,805 |
| Middle Eastern | 0.0164% | 6,082 |
| European (non-Finnish) | 0.000508% | 196,666 |
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
- SEC24D
- Protein
- p.Ala905=
- Coding
- c.2715C>T
- MANE Select
- NM_014822
- dbSNP
- rs762216451
- Type
- single nucleotide variant
- Location
- chr4:118731469 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.21 · 6 PDB
- Residue 905
- an α-helix
Similar variants
- SEC24D c.1181-1G>C Likely pathogenic ★★ same type
- SEC24D c.1824+1G>T Likely pathogenic ★★ same type
- SEC24D p.Arg993Ter Pathogenic/Likely pathogenic ★★ same type
- SEC24D p.Ser1015Phe Pathogenic ★★ same type
- SEC24D p.Ala218Val Uncertain significance ★★ ⚠ same type
- SEC24D p.Ala570Val Uncertain significance ★★ ⚠ same type
- SEC24D p.Ala774Asp Uncertain significance ★★ ⚠ same type
- SEC24D p.Ala94Thr Uncertain significance ★★ ⚠ 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/sec24d-p-ala905 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown