AP4M1 p.Ser254=
c.762G>A · rs774302896 · VCV210214
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
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 -0.22 | GERP -3.1, phastCons 0.003 |
| Overall | ||
| CADD | 9.964 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,860 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000744%
12/1,613,898 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,953 |
| South Asian | 0.0011% | 91,092 |
| European (non-Finnish) | 0.000678% | 147,502 |
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
- AP4M1
- Protein
- p.Ser254=
- Coding
- c.762G>A
- MANE Select
- NM_004722
- dbSNP
- rs774302896
- Type
- single nucleotide variant
- Location
- chr7:100105274 (GRCh38)
- Gene constraint
- LOEUF 1.106 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.16 · 6 PDB
- Residue 254
- the mhd domain; a β-strand
Similar variants
- AP4M1 p.Ser254Leu Uncertain significance ★ ⚠ same residue
- AP4M1 c.1137+1G>T Pathogenic/Likely pathogenic ★★ same type
- AP4M1 c.930-1G>C Likely pathogenic ★★ same type
- AP4M1 p.Arg268Ter Pathogenic ★★ same type
- AP4M1 p.Arg306Ter Pathogenic ★★ same type
- AP4M1 p.Arg318Ter Pathogenic ★★ same type
- AP4M1 p.Arg338Ter Pathogenic/Likely pathogenic ★★ same type
- AP4M1 p.Cys319Arg Pathogenic/Likely 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/ap4m1-p-ser254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown