NFASC p.Pro727=
c.2181C>T · rs12084475 · VCV3049745
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.565%, afr)
Conditions
1
NFASC-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.108 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -4.8 |
| Overall | ||
| CADD | 0.651 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.565%
African / African-American · 424/75,012 alleles
Filtering AF
0.521%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.503%
Overall
0.0315%
509/1,613,518 alleles · rare
exomes 258/1,461,250 · genomes 251/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.565% | 177 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,082 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0473% | 2,114 |
| Admixed American | 0.03% | 3,331 |
| East Asian | 0.0267% | 3,739 |
| Middle Eastern | 0.0165% | 6,062 |
| Finnishnot grpmax-eligible | 0.00156% | 63,992 |
| European (non-Finnish) | 0.000763% | 131,078 |
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
- NFASC
- Protein
- p.Pro727=
- Coding
- c.2181C>T
- MANE Select
- NM_001005388
- dbSNP
- rs12084475
- Type
- single nucleotide variant
- Location
- chr1:204980374 (GRCh38)
- Gene constraint
- LOEUF 0.362 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.23 · 2 PDB
- Residue 727
- the 'disordered' region
Disease context
NFASC-related disorder
Similar variants
- NFASC c.1831+11A>G Benign same condition
- NFASC c.2470+2131G>A Likely benign same condition
- NFASC c.3020-9G>A Likely benign same condition
- NFASC c.3290-9C>T Likely benign same condition
- NFASC c.536-4A>G Likely benign same condition
- NFASC c.*1C>T Likely benign same condition
- NFASC p.Ala1103= Benign same condition
- NFASC p.Ala986= Likely benign 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/nfasc-p-pro727 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown