Is TTC19 c.*195A>G pathogenic?

TTC19 c.195A>G is classified Conflicting classifications of pathogenicity in TTC19 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-07-09). Low-frequency (popmax 3.16%, afr); Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 c.*195A>G?

TTC19 c.*195A>G is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 c.*195A>G in the general population?

TTC19 c.*195A>G is low-frequency (popmax 3.16%, afr) (gnomAD).

TTC19 c.*195A>G

rs116412774 · VCV891497

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.16%, 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 -0.072	GERP -3.2
Non-coding constraint	Z 1.49	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	3.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.16% African / African-American · 1,790/56,578 alleles

Filtering AF 3.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.99%

Overall 0.297% 1,992/669,776 alleles · low-frequency exomes 605/517,518 · genomes 1,387/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.16%	32
Remaining individualsnot grpmax-eligible	0.24%	417
Admixed American	0.229%	436
Middle Eastern	0.0389%	2,570
European (non-Finnish)	0.00432%	23,159
South Asian	0.003%	33,285

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.*195A>G
MANE Select: NM_017775
dbSNP: rs116412774
Type: single nucleotide variant
Location: chr17:16027717 (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-195a-g (accessed [today's date]).

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