Is TTC19 p.Gln173Ter (c.517C>T) pathogenic?

TTC19 p.Gln173Ter (c.517C>T) is classified Pathogenic in TTC19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2011-03-01). Very rare (popmax 8.48e-05%, nfe); Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 p.Gln173Ter (c.517C>T)?

TTC19 p.Gln173Ter (c.517C>T) is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 p.Gln173Ter (c.517C>T) in the general population?

TTC19 p.Gln173Ter (c.517C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

TTC19 p.Gln173Ter

c.517C>T · rs387907094 · VCV31074

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

mitochondrial complex III deficiency nuclear type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	Δ0.31	donor loss · deltas
Pangolin	Δ0.42	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Overall
CADD	48.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,788 alleles

Overall 6.2e-05% 1/1,613,678 alleles · very rare exomes 1/1,461,450 · genomes 0/152,228 · joint denominator

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.Gln173Ter
Coding: c.517C>T
MANE Select: NM_017775
dbSNP: rs387907094
Type: single nucleotide variant
Location: chr17:16003885 (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-gln173ter (accessed [today's date]).

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