C1D p.Glu4=
c.12A>G · rs72906856 · VCV787002
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.51%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor loss, 16 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | phastCons 1 |
| Overall | ||
| CADD | 10.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.51%
African / African-American · 3,374/74,756 alleles
Filtering AF
4.39%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.33%
Overall
0.269%
4,322/1,609,026 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.51% | 22 |
| Ashkenazi Jewishnot grpmax-eligible | 1.04% | 96 |
| Remaining individualsnot grpmax-eligible | 0.37% | 271 |
| Admixed American | 0.353% | 283 |
| Middle Eastern | 0.116% | 863 |
| European (non-Finnish) | 0.016% | 6,268 |
| South Asian | 0.0067% | 14,927 |
| Finnishnot grpmax-eligible | 0.00157% | 63,722 |
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
- C1D
- Protein
- p.Glu4=
- Coding
- c.12A>G
- MANE Select
- NM_173177
- dbSNP
- rs72906856
- Type
- single nucleotide variant
- Location
- chr2:68047299 (GRCh38)
- Gene constraint
- LOEUF 0.826 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 88.37
- Residue 4
- the 'required for transcriptional repression' region
Similar variants
- LRP1 p.Ala1564Thr Uncertain significance ★★ same type
- LRP1 p.Arg228Gln Uncertain significance ★★ same type
- LRP1 p.Arg2440Trp Uncertain significance ★★ ⚠ same type
- LRP1 p.Arg539Gln Uncertain significance ★★ same type
- LRP1 p.Asp4483Tyr Uncertain significance ★★ ⚠ same type
- LRP1 p.Ser2907Pro Uncertain significance ★★ same type
- LRP1 p.Val3296Ile Uncertain significance ★★ ⚠ same type
- LRP1 c.10014+86A>G Benign ★★ 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/c1d-p-glu4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown