AGAP1 p.Asp541=
c.1623C>T · rs1346008352 · VCV2132583
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00678%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.319 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -9.4 | GERP -2.8 |
| Overall | ||
| CADD | 5.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00678%
East Asian · 3/44,230 alleles
Filtering AF
0.0018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000899%
Overall
0.000872%
14/1,605,058 alleles · very rare
exomes 12/1,456,034 · genomes 2/149,024 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00678% | 14,743 |
| South Asian | 0.00331% | 30,257 |
| African / African-American | 0.00272% | 36,726 |
| European (non-Finnish) | 0.00051% | 196,011 |
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
- AGAP1
- Protein
- p.Asp541=
- Coding
- c.1623C>T
- MANE Select
- NM_001037131
- dbSNP
- rs1346008352
- Type
- single nucleotide variant
- Location
- chr2:235968601 (GRCh38)
- Gene constraint
- LOEUF 0.366 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.01 · 2 PDB
- Residue 541
- the 'disordered' region; the ph domain
Similar variants
- AGAP1 p.Asp541Asn Uncertain significance ★ ⚠ same residue
- AGAP1 p.Ala418Ser Uncertain significance ★★ ⚠ same type
- AGAP1 p.Ala52Ser Uncertain significance ★★ ⚠ same type
- AGAP1 p.Ala570Gly Uncertain significance ★★ same type
- AGAP1 p.Ala809Ser Uncertain significance ★★ ⚠ same type
- AGAP1 p.Arg14Trp Uncertain significance ★★ ⚠ same type
- AGAP1 p.Arg313His Uncertain significance ★★ ⚠ same type
- AGAP1 p.Arg696Trp 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/agap1-p-asp541 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown