CARMIL2 p.Pro1046=
c.3138G>A · rs114594028 · VCV1166460
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.17%, 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 -2.7 | GERP -3.2 |
| Overall | ||
| CADD | 1.606 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.17%
South Asian · 3,516/84,354 alleles
Filtering AF
4.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.01%
Overall
1%
15,527/1,549,388 alleles · low-frequency
exomes 13,188/1,403,182 · genomes 2,339/146,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 4.17% | 24 |
| African / African-American | 3.67% | 27 |
| Ashkenazi Jewishnot grpmax-eligible | 1.55% | 64 |
| Remaining individualsnot grpmax-eligible | 1.04% | 96 |
| Finnishnot grpmax-eligible | 0.813% | 123 |
| European (non-Finnish) | 0.652% | 153 |
| Admixed American | 0.646% | 155 |
| Middle Eastern | 0.614% | 163 |
| Amishnot grpmax-eligible | 0.111% | 902 |
| East Asian | 0.00726% | 13,772 |
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
- CARMIL2
- Protein
- p.Pro1046=
- Coding
- c.3138G>A
- MANE Select
- NM_001013838
- dbSNP
- rs114594028
- Type
- single nucleotide variant
- Location
- chr16:67654166 (GRCh38)
- Gene constraint
- LOEUF 0.701 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.50
- Residue 1046
- the 'disordered' region; a UniProt-annotated variant site (in imd58; no detectable protein expression in patient's leukocytes; no effect on homodimerization)
Similar variants
- CARMIL2 c.1334+1G>T Likely pathogenic ★★ same type
- CARMIL2 c.2313+1G>A Likely pathogenic ★★ same type
- CARMIL2 c.871+1G>T Pathogenic ★★ same type
- CARMIL2 c.958+1G>A Likely pathogenic ★★ same type
- CARMIL2 p.Arg174Ter Pathogenic/Likely pathogenic ★★ same type
- CARMIL2 p.Asn530Lys Pathogenic/Likely pathogenic ★★ same type
- CARMIL2 p.Gln1379Ter Pathogenic/Likely pathogenic ★★ same type
- CARMIL2 p.Ser370Ter 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/carmil2-p-pro1046 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown