Is TTC19 p.Ala191= (c.573G>A) pathogenic?

TTC19 p.Ala191= (c.573G>A) is classified Benign in TTC19 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Common (popmax 11.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 p.Ala191= (c.573G>A)?

TTC19 p.Ala191= (c.573G>A) is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

TTC19 p.Ala191=

Q: How common is TTC19 p.Ala191= (c.573G>A) in the general population?

TTC19 p.Ala191= (c.573G>A) is common (popmax 11.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.573G>A · rs58517927 · VCV137767

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 11.2%, 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 0.75	GERP -3.4, phastCons 1
Overall
CADD	10.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.2% African / African-American · 8,418/74,994 alleles

Filtering AF 11% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.9%

Overall 0.616% 9,949/1,614,054 alleles · common exomes 5,085/1,461,738 · genomes 4,864/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.2%	9
Middle Eastern	0.858%	117
Remaining individualsnot grpmax-eligible	0.832%	120
Admixed American	0.786%	127
South Asian	0.121%	828
European (non-Finnish)	0.0308%	3,250
East Asian	0.0267%	3,741
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801

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.Ala191=
Coding: c.573G>A
MANE Select: NM_017775
dbSNP: rs58517927
Type: single nucleotide variant
Location: chr17:16004254 (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.Ala191Val Uncertain significance ★ ⚠ same residue
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

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-ala191 (accessed [today's date]).

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