WAC p.Pro437=
c.1311G>A · VCV4906968
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, 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 0.7 | GERP -1.9, phastCons 0.97 |
| Overall | ||
| CADD | 7.378 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,862 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000806%
13/1,613,718 alleles · very rare
exomes 9/1,461,776 · genomes 4/151,942 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,431 |
| Finnishnot grpmax-eligible | 0.00313% | 31,989 |
| Admixed American | 0.00167% | 59,972 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| South Asian | 0.0011% | 91,054 |
| European (non-Finnish) | 0.000508% | 196,664 |
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
- WAC
- Protein
- p.Pro437=
- Coding
- c.1311G>A
- MANE Select
- NM_016628
- Type
- single nucleotide variant
- Location
- chr10:28611796 (GRCh38)
- Gene constraint
- LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.71
- Residue 437
- a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic); the 'disordered' region
Similar variants
- WAC p.Pro437Leu Uncertain significance ★ ⚠ same residue
- WAC c.1437+1G>A Pathogenic/Likely pathogenic ★★ same type
- WAC c.1746+2T>C Pathogenic ★★ same type
- WAC c.381+1G>T Likely pathogenic ★★ same type
- WAC p.Arg151Ter Pathogenic ★★ same type
- WAC p.Arg47Ter Pathogenic ★★ same type
- WAC p.Arg513Ter Pathogenic ★★ same type
- WAC p.Arg550Ter Pathogenic ★★ 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/wac-p-pro437 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown