MFSD8 p.Phe75Val
c.223T>G · VCV4968616
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4228 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4228 | ambiguous |
|---|---|---|
| REVEL | 0.7 | pathogenic-leaning |
| SaProt | LLR -12.71 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 44 kb · p 0.0019 · regional, not allelic |
| Overall | ||
| CADD | 26.7 | 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
- MFSD8
- Protein
- p.Phe75Val
- Coding
- c.223T>G
- MANE Select
- NM_001371596
- Type
- single nucleotide variant
- Location
- chr4:127943968 (GRCh38)
- Gene constraint
- LOEUF 1.005 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.20
Similar variants
- MFSD8 p.Phe75= Likely benign ★ same residue
- MFSD8 c.1102+1G>A Likely pathogenic ★★ same type
- MFSD8 c.1102+2T>C Pathogenic/Likely pathogenic ★★ same type
- MFSD8 c.1350+2T>C Pathogenic/Likely pathogenic ★★ same type
- MFSD8 c.154+1G>A Likely pathogenic ★★ same type
- MFSD8 c.198+2T>C Pathogenic/Likely pathogenic ★★ same type
- MFSD8 c.439+2T>A Likely pathogenic ★★ same type
- MFSD8 c.440-2A>T Likely pathogenic ★★ 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/mfsd8-p-phe75val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown