NFASC p.Pro165=
c.495G>A · rs77635708 · VCV719373
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.16%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.049 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -6.3 | GERP -5.3 |
| Overall | ||
| CADD | 1.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.16%
African / African-American · 871/74,998 alleles
Filtering AF
1.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.07%
Overall
0.0621%
1,003/1,614,020 alleles · low-frequency
exomes 508/1,461,836 · genomes 495/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.16% | 86 |
| Remaining individualsnot grpmax-eligible | 0.0896% | 1,116 |
| Admixed American | 0.0717% | 1,395 |
| Middle Eastern | 0.066% | 1,514 |
| South Asian | 0.00549% | 18,214 |
| European (non-Finnish) | 0.00203% | 49,166 |
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.Pro165=
- Coding
- c.495G>A
- MANE Select
- NM_001005388
- dbSNP
- rs77635708
- Type
- single nucleotide variant
- Location
- chr1:204954911 (GRCh38)
- Gene constraint
- LOEUF 0.362 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.23 · 2 PDB
- Residue 165
- the ig-like c2-type 2 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-pro165 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown