NFASC p.Pro650=
c.1950C>T · rs192014745 · VCV3037351
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0934%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.173 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -4.8 |
| Overall | ||
| CADD | 0.393 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0934%
European (non-Finnish) · 1,077/1,153,456 alleles
Filtering AF
0.0887%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0868%
Overall
0.074%
1,157/1,564,180 alleles · ultra-rare
exomes 1,088/1,411,882 · genomes 69/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0934% | 1,071 |
| Remaining individualsnot grpmax-eligible | 0.0612% | 1,635 |
| Admixed American | 0.0407% | 2,457 |
| African / African-American | 0.0217% | 4,609 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00348% | 28,766 |
| Finnishnot grpmax-eligible | 0.00333% | 30,002 |
| East Asian | 0.00239% | 41,854 |
| South Asian | 0.00118% | 84,872 |
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.Pro650=
- Coding
- c.1950C>T
- MANE Select
- NM_001005388
- dbSNP
- rs192014745
- Type
- single nucleotide variant
- Location
- chr1:204979041 (GRCh38)
- Gene constraint
- LOEUF 0.362 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.23 · 2 PDB
- Residue 650
- the fibronectin type-iii 1 domain
Similar variants
- NFASC c.2593+5G>A Uncertain significance ★★ same type
- NFASC p.Ala253Thr Uncertain significance ★★ same type
- NFASC p.Arg133His Uncertain significance ★★ same type
- NFASC p.Arg436Gln Uncertain significance ★★ same type
- NFASC p.Asn655Asp Uncertain significance ★★ same type
- NFASC p.Asp1038Ala Uncertain significance ★★ same type
- NFASC p.Asp601Val Uncertain significance ★★ same type
- NFASC p.Gly23Arg Uncertain significance ★★ 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/nfasc-p-pro650 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown