Is TTC19 c.*335C>T pathogenic?

TTC19 c.335C>T is classified Conflicting classifications of pathogenicity in TTC19 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-06-01). Low-frequency (popmax 1.01%, nfe); Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 c.*335C>T?

TTC19 c.*335C>T is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 c.*335C>T in the general population?

TTC19 c.*335C>T is low-frequency (popmax 1.01%, nfe) (gnomAD).

TTC19 c.*335C>T

rs117087989 · VCV321955

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 1.01%, nfe)

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 0.13	GERP -1.4
Non-coding constraint	Z 1.49	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	3.879	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.01% European (non-Finnish) · 2,431/239,694 alleles

Filtering AF 0.981% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.967%

Overall 0.775% 3,676/474,376 alleles · low-frequency exomes 2,575/322,216 · genomes 1,101/152,160 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.03%	33
Finnishnot grpmax-eligible	1.58%	63
European (non-Finnish)grpmax	1.01%	99
Remaining individualsnot grpmax-eligible	0.928%	108
Admixed American	0.302%	331
African / African-American	0.116%	862
Amishnot grpmax-eligible	0.11%	912
South Asian	0.0727%	1,376

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.*335C>T
MANE Select: NM_017775
dbSNP: rs117087989
Type: single nucleotide variant
Location: chr17:16027857 (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-335c-t (accessed [today's date]).

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