ANKRD33 p.Pro416=
c.1248G>A · VCV3297439
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.001 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -4.3 |
| Overall | ||
| CADD | 0.497 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.0111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0105%
Overall
0.00997%
161/1,614,112 alleles · ultra-rare
exomes 155/1,461,892 · genomes 6/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| European (non-Finnish) | 0.0128% | 7,815 |
| South Asian | 0.00439% | 22,772 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| African / African-American | 0.00267% | 37,473 |
| Admixed American | 0.00167% | 60,004 |
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
- ANKRD33
- Protein
- p.Pro416=
- Coding
- c.1248G>A
- MANE Select
- NM_182608
- Type
- single nucleotide variant
- Location
- chr12:51891194 (GRCh38)
- Gene constraint
- LOEUF 1.351 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.72
- Residue 416
- the 'disordered' region
Similar variants
- ANKRD33 p.Ala113Val Uncertain significance ★ ⚠ same type
- ANKRD33 p.Ala124Val Uncertain significance ★ ⚠ same type
- ANKRD33 p.Ala203Val Uncertain significance ★ same type
- ANKRD33 p.Ala207Val Uncertain significance ★ ⚠ same type
- ANKRD33 p.Ala407Thr Uncertain significance ★ ⚠ same type
- ANKRD33 p.Arg195His Uncertain significance ★ ⚠ same type
- ANKRD33 p.Arg199Trp Uncertain significance ★ ⚠ same type
- ANKRD33 p.Arg210Gln 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/ankrd33-p-pro416 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown