DOC2B p.Leu171=
c.513G>T · VCV4822660
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0333%, sas)
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 -0.48 | phastCons 0.031 |
| Overall | ||
| CADD | 8.318 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0333%
South Asian · 28/84,208 alleles
Filtering AF
0.0236%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0204%
Overall
0.002%
31/1,553,056 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0333% | 3,007 |
| Middle Eastern | 0.0167% | 5,996 |
| Remaining individualsnot grpmax-eligible | 0.00332% | 30,100 |
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
- DOC2B
- Protein
- p.Leu171=
- Coding
- c.513G>T
- MANE Select
- NM_003585
- Type
- single nucleotide variant
- Location
- chr17:164145 (GRCh38)
- Gene constraint
- LOEUF 1.371 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.21
- Residue 171
- the c2 1 domain
Similar variants
- DOC2B p.Ala103Thr Uncertain significance ★ ⚠ same type
- DOC2B p.Ala295Thr Uncertain significance ★ ⚠ same type
- DOC2B p.Ala54Glu Uncertain significance ★ ⚠ same type
- DOC2B p.Ala58Ser Uncertain significance ★ ⚠ same type
- DOC2B p.Ala63Thr Uncertain significance ★ ⚠ same type
- DOC2B p.Arg186Cys Uncertain significance ★ ⚠ same type
- DOC2B p.Arg186His Uncertain significance ★ ⚠ same type
- DOC2B p.Arg209His 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/doc2b-p-leu171 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown