Is TTC19 p.Leu9= (c.25C>T) pathogenic?

TTC19 p.Leu9= (c.25C>T) is classified Conflicting classifications of pathogenicity in TTC19 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-12-31). Ultra-rare (popmax 0.0126%, amr); Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 p.Leu9= (c.25C>T)?

TTC19 p.Leu9= (c.25C>T) is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 p.Leu9= (c.25C>T) in the general population?

TTC19 p.Leu9= (c.25C>T) is ultra-rare (popmax 0.0126%, amr) (gnomAD).

TTC19 p.Leu9=

c.25C>T · rs568088809 · VCV321940

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, amr)

Conditions

mitochondrial complex III deficiency nuclear type 2

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 -1.2	GERP -3.3
Overall
CADD	4.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0126% Admixed American · 5/39,640 alleles

Filtering AF 0.00491% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00317%

Overall 0.00048% 7/1,457,710 alleles · ultra-rare exomes 5/1,305,512 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0126%	7,928
Remaining individualsnot grpmax-eligible	0.00178%	56,236
European (non-Finnish)	8.99e-05%	1,112,806

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: TTC19
Protein: p.Leu9=
Coding: c.25C>T
MANE Select: NM_017775
dbSNP: rs568088809
Type: single nucleotide variant
Location: chr17:15999873 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.28

Full TTC19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex III deficiency nuclear type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTC19 p.Gln195Ter Pathogenic/Likely pathogenic ★★ same condition
TTC19 p.Leu185Pro Pathogenic/Likely pathogenic ★★ same condition
TTC19 p.Leu219Ter Pathogenic ★★ same condition
TTC19 c.581+4A>C Uncertain significance ★★ same condition
TTC19 c.994+3A>T Uncertain significance ★★ same condition
TTC19 p.Ala122Thr Uncertain significance ★★ ⚠ same condition
TTC19 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg102Gly Uncertain significance ★★ ⚠ 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/ttc19-p-leu9 (accessed [today's date]).

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