NDNF p.Phe255Ser
c.764T>C · VCV4556617
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.7959 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.7959 | likely pathogenic |
|---|---|---|
| REVEL | 0.219 | benign-leaning |
| SaProt | LLR -6.99 | tolerated |
| ⇒ AlphaMissense calls this damaging; REVEL and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.3 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.92 | unconstrained · MANE · 9,570 bp · p 0.052 · regional, not allelic |
| Overall | ||
| CADD | 23.9 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- NDNF
- Protein
- p.Phe255Ser
- Coding
- c.764T>C
- MANE Select
- NM_024574
- Type
- single nucleotide variant
- Location
- chr4:121037207 (GRCh38)
- Gene constraint
- LOEUF 0.556 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 78.58
- Residue 255
- a UniProt-annotated variant site (in hh25; loss of protein expression)
Similar variants
- NDNF p.Lys275Asn Uncertain significance ★★ ⚠ same type
- NDNF p.Lys341Glu Uncertain significance ★★ ⚠ same type
- NDNF p.Asp313= Benign ★★ same type
- NDNF p.Leu145= Benign ★★ same type
- NDNF p.Leu345= Benign ★★ same type
- NDNF p.Leu523= Benign ★★ same type
- NDNF p.Lys62= Benign ★★ same type
- NDNF p.Ser464= Benign ★★ 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/ndnf-p-phe255ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown