Is SURF1 p.Phe74fs (c.219del) pathogenic?

SURF1 p.Phe74fs (c.219del) is classified Likely pathogenic in SURF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). Associated with mitochondrial complex IV deficiency, nuclear type 1.

What condition is associated with SURF1 p.Phe74fs (c.219del)?

SURF1 p.Phe74fs (c.219del) is associated with mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

How is Isolated cytochrome C oxidase deficiency inherited?

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

SURF1 p.Phe74fs

c.219del · VCV3775466

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

mitochondrial complex IV deficiency, nuclear type 1

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 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 2, phastCons 1

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

Variant & gene context

Gene: SURF1
Protein: p.Phe74fs
Coding: c.219del
MANE Select: NM_003172
Type: Deletion
Location: chr9:133354845 (GRCh38)
Gene constraint: LOEUF 1.559 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.62

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

Disease context

mitochondrial complex IV deficiency, nuclear type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

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.Leu7fs Pathogenic/Likely pathogenic ★★ same condition
SURF1 p.Lys185fs Pathogenic/Likely pathogenic ★★ same condition
SURF1 p.Met1_Ala5del 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-phe74fs (accessed [today's date]).

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