APCDD1L p.Ala22=
c.66G>A · VCV4641609
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00244%, 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 -6.9 | GERP -4 |
| Overall | ||
| CADD | 0.389 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00244%
East Asian · 1/41,002 alleles
Filtering AF
0.000128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.3e-05%
Overall
0.00052%
8/1,539,254 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00244% | 41,002 |
| Finnishnot grpmax-eligible | 0.00201% | 49,846 |
| South Asian | 0.00119% | 83,882 |
| European (non-Finnish) | 0.000436% | 229,322 |
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
- APCDD1L
- Protein
- p.Ala22=
- Coding
- c.66G>A
- MANE Select
- NM_153360
- Type
- single nucleotide variant
- Location
- chr20:58470731 (GRCh38)
- Gene constraint
- LOEUF 1.86 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.31
Similar variants
- APCDD1L p.Ala141Val Uncertain significance ★ ⚠ same type
- APCDD1L p.Ala159Glu Uncertain significance ★ ⚠ same type
- APCDD1L p.Ala246Ser Uncertain significance ★ ⚠ same type
- APCDD1L p.Ala333Thr Uncertain significance ★ ⚠ same type
- APCDD1L p.Ala3Ser Uncertain significance ★ ⚠ same type
- APCDD1L p.Arg139His Uncertain significance ★ ⚠ same type
- APCDD1L p.Arg139Pro Uncertain significance ★ ⚠ same type
- APCDD1L p.Arg153Cys 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/apcdd1l-p-ala22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown