TSFM p.Phe10=

Q: Is TSFM p.Phe10= (c.30T>C) pathogenic?

TSFM p.Phe10= (c.30T>C) is classified Benign in TSFM (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 69.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3.

Q: What condition is associated with TSFM p.Phe10= (c.30T>C)?

TSFM p.Phe10= (c.30T>C) is associated with fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (ClinVar).

Q: How common is TSFM p.Phe10= (c.30T>C) in the general population?

TSFM p.Phe10= (c.30T>C) is common (popmax 69.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 inherited?

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

c.30T>C · rs10747783 · VCV310006

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 69.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3

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 -0.2	GERP -1.6
Overall
CADD	8.429	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 69.7% East Asian · 30,506/43,756 alleles

Filtering AF 69.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 68.8%

Overall 33.8% 539,274/1,594,138 alleles · common exomes 497,089/1,442,058 · genomes 42,185/152,080 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	69.7%	1
South Asian	55.2%	2
Amishnot grpmax-eligible	38.4%	3
Finnishnot grpmax-eligible	36.1%	3
Remaining individualsnot grpmax-eligible	33.1%	3
European (non-Finnish)	32.6%	3
Admixed American	31.6%	3
Ashkenazi Jewishnot grpmax-eligible	28.8%	3
Middle Eastern	19.8%	5
African / African-American	10.3%	10

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: TSFM
Protein: p.Phe10=
Coding: c.30T>C
MANE Select: NM_005726
dbSNP: rs10747783
Type: single nucleotide variant
Location: chr12:57782831 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.87 · 1 PDB

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

Disease context

fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

TSFM p.Phe10fs Pathogenic/Likely pathogenic ★★ same residue
TSFM c.231+1G>A Likely pathogenic ★★ same condition
TSFM c.232-2A>G Likely pathogenic ★★ same condition
TSFM c.484-1G>A Likely pathogenic ★★ same condition
TSFM c.484-1G>T Likely pathogenic ★★ same condition
TSFM c.57+1G>A Likely pathogenic ★★ same condition
TSFM c.571+1G>C Pathogenic/Likely pathogenic ★★ same condition
TSFM p.Arg201Ter 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/tsfm-p-phe10 (accessed [today's date]).

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