Is SURF1 p.Ala24= (c.72C>T) pathogenic?

SURF1 p.Ala24= (c.72C>T) is classified Likely benign in SURF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). Very rare (popmax 0.00359%, sas); Associated with Leigh syndrome.

What condition is associated with SURF1 p.Ala24= (c.72C>T)?

SURF1 p.Ala24= (c.72C>T) is associated with Leigh syndrome (ClinVar).

How common is SURF1 p.Ala24= (c.72C>T) in the general population?

SURF1 p.Ala24= (c.72C>T) is very rare (popmax 0.00359%, sas) (gnomAD).

How is Leigh syndrome inherited?

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

SURF1 p.Ala24=

c.72C>T · rs1163546025 · VCV2877063

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00359%, sas)

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 2.8	GERP 0.22, phastCons 0.15
Overall
CADD	13.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00359% South Asian · 3/83,512 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000465%

Overall 0.000327% 5/1,526,980 alleles · very rare exomes 4/1,375,082 · genomes 1/151,898 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00359%	27,837
Remaining individualsnot grpmax-eligible	0.00168%	59,480
European (non-Finnish)	8.74e-05%	1,143,773

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.Ala24=
Coding: c.72C>T
MANE Select: NM_003172
dbSNP: rs1163546025
Type: single nucleotide variant
Location: chr9:133356303 (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

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.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
SURF1 c.752-3C>G 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-ala24 (accessed [today's date]).

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