Is TTC19 c.*1012T>C pathogenic?

TTC19 c.1012T>C is classified Benign in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Common (popmax 6.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 c.*1012T>C?

TTC19 c.*1012T>C is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

TTC19 c.*1012T>C

Q: How common is TTC19 c.*1012T>C in the general population?

TTC19 c.*1012T>C is common (popmax 6.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs57322947 · VCV889321

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.4%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.23	GERP 0.42
Overall
CADD	2.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.4% African / African-American · 3,205/50,084 alleles

Filtering AF 6.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.14%

Overall 0.764% 3,470/454,034 alleles · common exomes 696/301,788 · genomes 2,774/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.4%	16
Remaining individualsnot grpmax-eligible	0.526%	190
Middle Eastern	0.416%	241
Admixed American	0.331%	302
South Asian	0.0124%	8,060
European (non-Finnish)	0.011%	9,071

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.*1012T>C
MANE Select: NM_017775
dbSNP: rs57322947
Type: single nucleotide variant
Location: chr17:16028534 (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-1012t-c (accessed [today's date]).

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