NFASC p.Ser862=
c.2586C>T · rs370114778 · VCV2639841
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -4.5 |
| Overall | ||
| CADD | 15.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00863%
Overall
0.00855%
138/1,613,882 alleles · ultra-rare
exomes 133/1,461,592 · genomes 5/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| European (non-Finnish) | 0.0108% | 9,289 |
| African / African-American | 0.008% | 12,507 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,247 |
| East Asian | 0.00223% | 44,878 |
| South Asian | 0.0011% | 91,084 |
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.Ser862=
- Coding
- c.2586C>T
- MANE Select
- NM_001005388 · reported on NM_001160331
- dbSNP
- rs370114778
- Type
- single nucleotide variant
- Location
- chr1:204984109 (GRCh38)
- Gene constraint
- LOEUF 0.362 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.23 · 2 PDB
- Residue 862
- the fibronectin type-iii 3 domain; 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-ser862 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown