Is TTC19 c.*219C>T pathogenic?

TTC19 c.219C>T is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-28). Very rare (popmax 0.00361%, afr); Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 c.*219C>T?

TTC19 c.*219C>T is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 c.*219C>T in the general population?

TTC19 c.*219C>T is very rare (popmax 0.00361%, afr) (gnomAD).

TTC19 c.*219C>T

rs986681161 · VCV891498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00361%, afr)

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 -0.11	GERP -3.3, phastCons 0.03
Non-coding constraint	Z 1.49	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	5.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00361% African / African-American · 2/55,372 alleles

Filtering AF 0.00137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00102%

Overall 0.00178% 11/617,758 alleles · very rare exomes 6/465,740 · genomes 5/152,018 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00361%	27,686
European (non-Finnish)	0.0027%	37,049

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
Coding: c.*219C>T
MANE Select: NM_017775
dbSNP: rs986681161
Type: single nucleotide variant
Location: chr17:16027741 (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-c-star-219c-t (accessed [today's date]).

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