CFLAR p.Val375=
c.1125G>A · rs151223777 · VCV773850
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.29%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.75 | GERP -3.5, phastCons 0.001 |
| Overall | ||
| CADD | 2.894 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.29%
Admixed American · 1,972/60,004 alleles
Filtering AF
3.17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.12%
Overall
0.202%
3,256/1,614,100 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 3.29% | 30 |
| East Asian | 1.76% | 57 |
| Remaining individualsnot grpmax-eligible | 0.126% | 791 |
| African / African-American | 0.0653% | 1,531 |
| European (non-Finnish) | 0.0299% | 3,343 |
| Finnishnot grpmax-eligible | 0.0125% | 8,004 |
| South Asian | 0.00549% | 18,216 |
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
- CFLAR
- Protein
- p.Val375=
- Coding
- c.1125G>A
- MANE Select
- NM_003879
- dbSNP
- rs151223777
- Type
- single nucleotide variant
- Location
- chr2:201160763 (GRCh38)
- Gene constraint
- LOEUF 0.397 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.84 · 17 PDB
- Residue 375
- the 'interaction with casp8 subunits p18 and p10' region; the 'interaction with casp8' region; the 'not proteolytically processed and involved in apoptosis inhibition' region; the 'interaction with traf1 and traf2' region; the 'interaction with casp3' region
Similar variants
- CFLAR p.Leu203Ile Benign ★★ same type
- CFLAR p.Ala178Thr Uncertain significance ★ ⚠ same type
- CFLAR p.Ala349Ser Uncertain significance ★ ⚠ same type
- CFLAR p.Arg303Ter Uncertain significance ★ same type
- CFLAR p.Arg315Gln Uncertain significance ★ ⚠ same type
- CFLAR p.Arg397Pro Uncertain significance ★ ⚠ same type
- CFLAR p.Asn199Ser Uncertain significance ★ ⚠ same type
- CFLAR p.Asn205His 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/cflar-p-val375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown