NFASC p.Ala503=
c.1509C>T · rs16854838 · VCV777984
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 7.12%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.024 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP 2.5, phastCons 1 |
| Overall | ||
| CADD | 13.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.12%
African / African-American · 5,339/75,030 alleles
Filtering AF
6.96%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.89%
Overall
0.464%
7,485/1,614,212 alleles · common
exomes 4,229/1,461,884 · genomes 3,256/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.12% | 14 |
| Middle Eastern | 1.11% | 90 |
| Admixed American | 0.875% | 114 |
| Remaining individualsnot grpmax-eligible | 0.79% | 127 |
| Ashkenazi Jewishnot grpmax-eligible | 0.601% | 166 |
| European (non-Finnish) | 0.0731% | 1,367 |
| South Asian | 0.0176% | 5,693 |
| Finnishnot grpmax-eligible | 0.00312% | 32,024 |
| East Asian | 0.00223% | 44,888 |
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.Ala503=
- Coding
- c.1509C>T
- MANE Select
- NM_001005388
- dbSNP
- rs16854838
- Type
- single nucleotide variant
- Location
- chr1:204974774 (GRCh38)
- Gene constraint
- LOEUF 0.362 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.23 · 2 PDB
- Residue 503
- the ig-like c2-type 5 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-ala503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown