Is SURF1 p.Phe290fs (c.870del) pathogenic?

SURF1 p.Phe290fs (c.870del) is classified Pathogenic/Likely pathogenic in SURF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-01). No gnomAD frequency available for this variant; Associated with Leigh syndrome.

What condition is associated with SURF1 p.Phe290fs (c.870del)?

SURF1 p.Phe290fs (c.870del) is associated with Leigh syndrome (ClinVar).

How common is SURF1 p.Phe290fs (c.870del) in the general population?

SURF1 p.Phe290fs (c.870del) is no gnomAD frequency available for this variant (gnomAD).

How is Leigh syndrome inherited?

Typically Autosomal recessive, Mitochondrial inheritance (Orphanet). A genetic counselor can assess individual risk for a family.

SURF1 p.Phe290fs

c.870del · rs782061187 · VCV2726031

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 0.24, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SURF1
Protein: p.Phe290fs
Coding: c.870del
MANE Select: NM_003172
dbSNP: rs782061187
Type: Deletion
Location: chr9:133351946 (GRCh38)
Gene constraint: LOEUF 1.559 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.62
Residue 290: a UniProt-annotated variant site (in mc4dn1; uncertain significance)

Full SURF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leigh syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leigh syndrome (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance, X-linked recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

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
SURF1 p.Leu62fs Pathogenic/Likely pathogenic ★★ same condition
SURF1 p.Leu7fs Pathogenic/Likely pathogenic ★★ same condition
SURF1 p.Lys185fs 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-phe290fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown