SEC24D p.Ala950=
c.2850A>G · rs146754256 · VCV796018
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0421%, nfe)
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 -2.9 | GERP -2.6 |
| Overall | ||
| CADD | 8.767 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0421%
European (non-Finnish) · 497/1,179,680 alleles
Filtering AF
0.039%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.0323%
521/1,613,712 alleles · ultra-rare
exomes 503/1,461,462 · genomes 18/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0421% | 2,374 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,675 |
| African / African-American | 0.00534% | 18,736 |
| South Asian | 0.0022% | 45,545 |
| Admixed American | 0.00167% | 60,004 |
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.Ala950=
- Coding
- c.2850A>G
- MANE Select
- NM_014822
- dbSNP
- rs146754256
- Type
- single nucleotide variant
- Location
- chr4:118731334 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.21 · 6 PDB
- Residue 950
- 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-ala950 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown