ANKH p.Leu228=
c.684G>A · rs200119947 · VCV1168320
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0758%, eas)
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 1.4 | GERP 0.7, phastCons 1 |
| Overall | ||
| CADD | 8.438 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0758%
East Asian · 34/44,884 alleles
Filtering AF
0.0557%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0488%
Overall
0.00242%
39/1,614,230 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0758% | 1,320 |
| African / African-American | 0.004% | 25,019 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 8.47e-05% | 1,180,048 |
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
- ANKH
- Protein
- p.Leu228=
- Coding
- c.684G>A
- MANE Select
- NM_054027
- dbSNP
- rs200119947
- Type
- single nucleotide variant
- Location
- chr5:14751072 (GRCh38)
- Gene constraint
- LOEUF 0.463 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.57
Similar variants
- ANKH c.1142-4A>G Pathogenic/Likely pathogenic ★★ same type
- ANKH c.96+5G>A Uncertain significance ★★ same type
- ANKH c.*3752G>A Uncertain significance ★★ same type
- ANKH p.Ala136Thr Uncertain significance ★★ ⚠ same type
- ANKH p.Ala201Thr Uncertain significance ★★ ⚠ same type
- ANKH p.Ala448Thr Uncertain significance ★★ ⚠ same type
- ANKH p.Arg453Gln Uncertain significance ★★ ⚠ same type
- ANKH p.Asn306Asp 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/ankh-p-leu228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown