SURF1 p.Phe181fs
c.537del · VCV4752269
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Leigh syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 9 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SURF1
- Protein
- p.Phe181fs
- Coding
- c.537del
- MANE Select
- NM_003172
- Type
- Deletion
- Location
- chr9:133352745 (GRCh38)
- Gene constraint
- LOEUF 1.559 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.62
- Residue 181
- a UniProt-annotated variant site (in mc4dn1; uncertain significance)
Disease context
Leigh syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Leigh syndrome (Orphanet):
- Inheritance
- Autosomal recessive, Mitochondrial inheritance, X-linked recessive
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- SURF1 p.Phe181= Benign/Likely benign ★★ same residue
- SURF1 p.Phe181Cys Uncertain significance ★ ⚠ same residue
- SURF1 p.Phe181Tyr Uncertain significance ★ ⚠ same residue
- SURF1 c.515+1del Pathogenic/Likely pathogenic ★★ same condition
- SURF1 p.Arg123fs Pathogenic ★★ same condition
- SURF1 p.Asn269fs Pathogenic/Likely pathogenic ★★ same condition
- SURF1 p.Gln251fs Pathogenic ★★ same condition
- SURF1 p.Glu211fs Pathogenic/Likely pathogenic ★★ same condition
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/surf1-p-phe181fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown