CARMIL2 p.Ala754=
c.2262C>T · VCV4741754
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7 | GERP -3.5 |
| Overall | ||
| CADD | 0.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,888 alleles
Filtering AF
0.000953%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.0013%
21/1,613,398 alleles · very rare
exomes 18/1,461,210 · genomes 3/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,888 |
| European (non-Finnish) | 0.00153% | 65,549 |
| African / African-American | 0.00133% | 74,918 |
| South Asian | 0.0011% | 91,084 |
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.Ala754=
- Coding
- c.2262C>T
- MANE Select
- NM_001013838
- Type
- single nucleotide variant
- Location
- chr16:67651264 (GRCh38)
- Gene constraint
- LOEUF 0.701 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.50
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-ala754 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown