ALMS1 p.Arg4066=
c.12198G>A · rs199603690 · VCV550031
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
Conditions
2
Cardiovascular phenotype
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 2.4 | GERP -0.16, phastCons 1 |
| Overall | ||
| CADD | 8.579 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,062 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0294%
Overall
0.00427%
69/1,614,168 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| South Asian | 0.0242% | 4,140 |
| African / African-American | 0.02% | 5,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| European (non-Finnish) | 0.00186% | 53,637 |
| Admixed American | 0.00167% | 60,030 |
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
- ALMS1
- Protein
- p.Arg4066=
- Coding
- c.12198G>A
- MANE Select
- NM_001378454
- dbSNP
- rs199603690
- Type
- single nucleotide variant
- Location
- chr2:73602268 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 4066
- the 'alms motif' region
Similar variants
- ALMS1 c.10079-1G>C Likely pathogenic ★★ same condition
- ALMS1 c.10214-2A>G Likely pathogenic ★★ same condition
- ALMS1 c.10384+1G>A Likely pathogenic ★★ same condition
- ALMS1 c.10385-2A>G Pathogenic ★★ same condition
- ALMS1 c.11547+3A>T Likely pathogenic ★★ same condition
- ALMS1 c.11668+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ALMS1 c.11669-1G>A Pathogenic ★★ same condition
- ALMS1 c.11669-1G>C Pathogenic/Likely pathogenic ★★ same condition
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/alms1-p-arg4066 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown