CGREF1 p.Ala127Val
c.380C>T · rs377330694 · VCV2341113
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0088%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.064 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -3, phastCons 0.023 |
| Overall | ||
| CADD | 8.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0088%
Admixed American · 5/56,832 alleles
Filtering AF
0.0034%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00246%
Overall
0.00333%
53/1,593,160 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0088% | 11,366 |
| Remaining individualsnot grpmax-eligible | 0.00649% | 15,409 |
| European (non-Finnish) | 0.00367% | 27,215 |
| African / African-American | 0.00135% | 74,304 |
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
- CGREF1
- Protein
- p.Ala127Val
- Coding
- c.380C>T
- MANE Select
- NM_006569 · reported on NM_001166240
- dbSNP
- rs377330694
- Type
- single nucleotide variant
- Location
- chr2:27099803 (GRCh38)
- Gene constraint
- LOEUF 1.364 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.75
- Residue 127
- a binding site; the ef-hand 2 domain
Similar variants
- KHK c.*469G>A Uncertain significance ★★ same type
- KHK p.Ala230Thr Uncertain significance ★★ ⚠ same type
- KHK p.Glu276Lys Uncertain significance ★★ ⚠ same type
- KHK c.*540G>C Benign ★★ same type
- KHK c.*580T>C Benign ★★ same type
- KHK c.*754T>C Benign ★★ same type
- KHK c.*767C>T Benign ★★ same type
- KHK c.*79G>A 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/cgref1-p-ala127val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown