CDH16 p.Leu377=
c.1131C>T · rs76542431 · VCV720839
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.82%, afr)
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 -2 | GERP -3.1 |
| Overall | ||
| CADD | 0.864 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.82%
African / African-American · 1,367/75,036 alleles
Filtering AF
1.74%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.71%
Overall
0.0943%
1,521/1,613,706 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.82% | 55 |
| Admixed American | 0.122% | 822 |
| Remaining individualsnot grpmax-eligible | 0.102% | 977 |
| Middle Eastern | 0.0495% | 2,021 |
| South Asian | 0.0022% | 45,540 |
| European (non-Finnish) | 0.00102% | 98,335 |
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
- CDH16
- Protein
- p.Leu377=
- Coding
- c.1131C>T
- MANE Select
- NM_004062
- dbSNP
- rs76542431
- Type
- single nucleotide variant
- Location
- chr16:66912815 (GRCh38)
- Gene constraint
- LOEUF 1.079 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.17
- Residue 377
- the cadherin 4 domain
Similar variants
- CDH16 p.Arg717His Benign ★★ same type
- CDH16 p.Ala133Ser Uncertain significance ★ ⚠ same type
- CDH16 p.Ala159Val Uncertain significance ★ ⚠ same type
- CDH16 p.Ala173Thr Uncertain significance ★ ⚠ same type
- CDH16 p.Ala202Val Uncertain significance ★ ⚠ same type
- CDH16 p.Ala20Thr Uncertain significance ★ ⚠ same type
- CDH16 p.Ala23Thr Uncertain significance ★ ⚠ same type
- CDH16 p.Ala425Thr 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/cdh16-p-leu377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown