SEC24D p.Pro59=
c.177G>A · rs149044753 · VCV1576088
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0268%, afr)
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 -4.6 | GERP -3.2 |
| Overall | ||
| CADD | 0.603 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0268%
African / African-American · 20/74,530 alleles
Filtering AF
0.0178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0148%
Overall
0.00696%
112/1,608,192 alleles · ultra-rare
exomes 95/1,456,046 · genomes 17/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0268% | 3,727 |
| European (non-Finnish) | 0.00722% | 13,855 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,738 |
| East Asian | 0.00225% | 44,508 |
| South Asian | 0.00222% | 44,987 |
| Admixed American | 0.0017% | 58,872 |
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.Pro59=
- Coding
- c.177G>A
- MANE Select
- NM_014822
- dbSNP
- rs149044753
- Type
- single nucleotide variant
- Location
- chr4:118824691 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.21 · 6 PDB
- Residue 59
- the 'disordered' region
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-pro59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown