Is TTC19 c.*971G>A pathogenic?

TTC19 c.971G>A is classified Likely benign in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Common (popmax 9.63%, 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.*971G>A?

TTC19 c.*971G>A is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

TTC19 c.*971G>A

Q: How common is TTC19 c.*971G>A in the general population?

TTC19 c.*971G>A is common (popmax 9.63%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs73981414 · VCV321965

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 9.63%, 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 -0.76	GERP 0.37
Overall
CADD	1.374	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.63% African / African-American · 4,822/50,070 alleles

Filtering AF 9.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.31%

Overall 4.21% 19,099/454,004 alleles · common exomes 11,354/301,792 · genomes 7,745/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.63%	10
East Asian	7.38%	14
Admixed American	5.03%	20
South Asian	4.98%	20
Middle Eastern	4.64%	22
Remaining individualsnot grpmax-eligible	4.18%	24
Finnishnot grpmax-eligible	3.85%	26
Ashkenazi Jewishnot grpmax-eligible	2.74%	36
European (non-Finnish)	2.58%	39

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.*971G>A
MANE Select: NM_017775
dbSNP: rs73981414
Type: single nucleotide variant
Location: chr17:16028493 (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-971g-a (accessed [today's date]).

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