NFASC p.Pro1069=
c.3207C>T · rs538088087 · VCV3042744
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0282%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 16.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0282%
African / African-American · 21/74,598 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0158%
Overall
0.00554%
88/1,587,914 alleles · ultra-rare
exomes 72/1,435,606 · genomes 16/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0282% | 3,552 |
| East Asian | 0.0203% | 4,925 |
| Remaining individualsnot grpmax-eligible | 0.00985% | 10,148 |
| European (non-Finnish) | 0.00414% | 24,176 |
| South Asian | 0.00338% | 29,625 |
| Admixed American | 0.00168% | 59,642 |
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.Pro1069=
- Coding
- c.3207C>T
- MANE Select
- NM_001005388
- dbSNP
- rs538088087
- Type
- single nucleotide variant
- Location
- chr1:205002666 (GRCh38)
- Gene constraint
- LOEUF 0.362 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.23 · 2 PDB
- Residue 1069
- a UniProt-annotated variant site (in nedcpmd; uncertain significance; no protein expression)
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-pro1069 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown