NFASC p.Pro682Ser
c.2044C>T · rs748826047 · VCV3195955
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00445%, eas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.12 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.76 | unconstrained · MANE · 53 kb · p 8.7e-18 · regional, not allelic |
| Overall | ||
| CADD | 24.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00445%
East Asian · 2/44,906 alleles
Filtering AF
0.000738%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000186%
3/1,613,956 alleles · very rare
exomes 0/1,461,766 · genomes 3/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00445% | 22,453 |
| European (non-Finnish) | 8.47e-05% | 1,180,013 |
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.Pro682Ser
- Coding
- c.2044C>T
- MANE Select
- NM_001005388
- dbSNP
- rs748826047
- Type
- single nucleotide variant
- Location
- chr1:204979427 (GRCh38)
- Gene constraint
- LOEUF 0.362 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.23 · 2 PDB
- Residue 682
- the fibronectin type-iii 1 domain
Similar variants
- NFASC p.Ala253Thr Uncertain significance ★★ same condition
- NFASC p.Arg133His Uncertain significance ★★ same condition
- NFASC p.Asp1038Ala Uncertain significance ★★ same condition
- NFASC p.Asp601Val Uncertain significance ★★ same condition
- NFASC p.Gly23Arg Uncertain significance ★★ same condition
- NFASC p.Leu287Phe Uncertain significance ★★ same condition
- NFASC p.Thr973Ala Uncertain significance ★★ same condition
- NFASC p.Val532Leu Uncertain significance ★★ 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-pro682ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown