SEC24D p.Ser449=
c.1347A>G · rs191460150 · VCV708519
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0385%, amr)
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 -9.3 | GERP -5.7 |
| Overall | ||
| CADD | 0.782 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0385%
Admixed American · 23/59,730 alleles
Filtering AF
0.0262%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0233%
Overall
0.0218%
352/1,611,770 alleles · ultra-rare
exomes 326/1,459,456 · genomes 26/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0385% | 2,597 |
| European (non-Finnish) | 0.0267% | 3,741 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,458 |
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.Ser449=
- Coding
- c.1347A>G
- MANE Select
- NM_014822
- dbSNP
- rs191460150
- Type
- single nucleotide variant
- Location
- chr4:118757795 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.21 · 6 PDB
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-ser449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown