Is SURF1 p.Phe293= (c.879C>T) pathogenic?

SURF1 p.Phe293= (c.879C>T) is classified Likely benign in SURF1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.0186%, nfe); Associated with Leigh syndrome.

What condition is associated with SURF1 p.Phe293= (c.879C>T)?

SURF1 p.Phe293= (c.879C>T) is associated with Leigh syndrome (ClinVar).

How common is SURF1 p.Phe293= (c.879C>T) in the general population?

SURF1 p.Phe293= (c.879C>T) is ultra-rare (popmax 0.0186%, nfe) (gnomAD).

How is Leigh syndrome inherited?

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

SURF1 p.Phe293=

c.879C>T · rs145088629 · VCV456667

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0186%, nfe)

Conditions

Leigh syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.072	GERP -2.1
Overall
CADD	0.604	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0186% European (non-Finnish) · 220/1,179,980 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.0146% 235/1,613,802 alleles · ultra-rare exomes 223/1,461,596 · genomes 12/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0186%	5,364
Remaining individualsnot grpmax-eligible	0.0144%	6,942
African / African-American	0.004%	24,973
South Asian	0.0033%	30,339

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SURF1
Protein: p.Phe293=
Coding: c.879C>T
MANE Select: NM_003172
dbSNP: rs145088629
Type: single nucleotide variant
Location: chr9:133351937 (GRCh38)
Gene constraint: LOEUF 1.559 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.62
Residue 293: 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 p.Phe293Leu Uncertain significance ★ ⚠ same residue
SURF1 c.106+1G>C Likely pathogenic ★★ same condition
SURF1 c.240+1G>T Pathogenic ★★ same condition
SURF1 c.324-11T>G Pathogenic/Likely pathogenic ★★ same condition
SURF1 c.516-2A>G Pathogenic ★★ same condition
SURF1 c.588+1G>C Pathogenic ★★ same condition
SURF1 c.751+1G>A Pathogenic ★★ same condition
SURF1 c.752-1G>C 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-phe293 (accessed [today's date]).

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