AHDC1 p.Pro540=
c.1620C>T · rs375899533 · VCV1266821
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.338%, sas)
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 0.12 | GERP 0.002, phastCons 0.75 |
| Overall | ||
| CADD | 5.545 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.338%
South Asian · 307/90,808 alleles
Filtering AF
0.307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.295%
Overall
0.0228%
366/1,607,306 alleles · rare
exomes 348/1,455,020 · genomes 18/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.338% | 296 |
| Middle Eastern | 0.0331% | 3,019 |
| Remaining individualsnot grpmax-eligible | 0.0241% | 4,145 |
| East Asian | 0.00671% | 14,909 |
| European (non-Finnish) | 0.00323% | 30,918 |
| African / African-American | 0.00134% | 74,886 |
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
- AHDC1
- Protein
- p.Pro540=
- Coding
- c.1620C>T
- MANE Select
- NM_001371928
- dbSNP
- rs375899533
- Type
- single nucleotide variant
- Location
- chr1:27550496 (GRCh38)
- Gene constraint
- LOEUF 0.168 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 38.82
- Residue 540
- a UniProt-annotated variant site (in xigis); a UniProt-annotated variant site (in xigis; impaired nuclear localization)
Similar variants
- AHDC1 p.Arg1272Ter Pathogenic ★★ same type
- AHDC1 p.Arg151Ter Pathogenic/Likely pathogenic ★★ same type
- AHDC1 p.Arg587Ter Pathogenic ★★ same type
- AHDC1 p.Arg688Ter Pathogenic ★★ same type
- AHDC1 p.Arg789Ter Pathogenic ★★ same type
- AHDC1 p.Arg925Ter Pathogenic/Likely pathogenic ★★ same type
- AHDC1 p.Gln332Ter Pathogenic ★★ same type
- AHDC1 p.Gln990Ter 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/ahdc1-p-pro540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown