Is TTC19 p.Arg3Trp (c.7C>T) pathogenic?

TTC19 p.Arg3Trp (c.7C>T) is classified Conflicting classifications of pathogenicity in TTC19 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-05-08). AlphaMissense: ambiguous (0.363); Rare (popmax 0.116%, sas); Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 p.Arg3Trp (c.7C>T)?

TTC19 p.Arg3Trp (c.7C>T) is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 p.Arg3Trp (c.7C>T) in the general population?

TTC19 p.Arg3Trp (c.7C>T) is rare (popmax 0.116%, sas) (gnomAD).

What do computational predictors say about TTC19 p.Arg3Trp (c.7C>T)?

AlphaMissense predicts ambiguous (score 0.363) — an in-silico prediction, not a clinical call.

TTC19 p.Arg3Trp

c.7C>T · rs756830714 · VCV215303

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.363 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

mitochondrial complex III deficiency nuclear type 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.363	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -10.07	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.1	GERP -2.5
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	19.46	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% South Asian · 95/81,730 alleles

Filtering AF 0.0973% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0903%

Overall 0.00818% 124/1,515,046 alleles · rare exomes 112/1,362,824 · genomes 12/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.116%	860
Middle Eastern	0.0437%	2,290
Remaining individualsnot grpmax-eligible	0.0085%	11,763
European (non-Finnish)	0.00184%	54,235
African / African-American	0.00142%	70,368

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.Arg3Trp
Coding: c.7C>T
MANE Select: NM_017775
dbSNP: rs756830714
Type: single nucleotide variant
Location: chr17:15999855 (GRCh38)

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

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-arg3trp (accessed [today's date]).

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