SEC24D p.Ser911=
c.2733C>A · rs76459466 · VCV1267254
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 19%, eas) — too common for a highly-penetrant pathogenic allele
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 -0.95 | GERP -3.6 |
| Overall | ||
| CADD | 6.261 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19%
East Asian · 8,515/44,858 alleles
Filtering AF
18.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 18.5%
Overall
1.35%
21,830/1,614,022 alleles · common
exomes 19,216/1,461,814 · genomes 2,614/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 19% | 5 |
| Middle Eastern | 5.72% | 17 |
| Ashkenazi Jewishnot grpmax-eligible | 4.94% | 20 |
| Remaining individualsnot grpmax-eligible | 2.55% | 39 |
| South Asian | 2.38% | 42 |
| African / African-American | 1.81% | 55 |
| Admixed American | 1.27% | 79 |
| Finnishnot grpmax-eligible | 0.989% | 101 |
| European (non-Finnish) | 0.423% | 237 |
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.Ser911=
- Coding
- c.2733C>A
- MANE Select
- NM_014822
- dbSNP
- rs76459466
- Type
- single nucleotide variant
- Location
- chr4:118731451 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.21 · 6 PDB
- Residue 911
- 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-ser911 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown