Is TTC19 p.Met1Val (c.1A>G) pathogenic?

TTC19 p.Met1Val (c.1A>G) is classified Conflicting classifications of pathogenicity in TTC19 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2022-05-04). Very rare (popmax 0.00578%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Met1Val (c.1A>G)?

TTC19 p.Met1Val (c.1A>G) is associated with Inborn genetic diseases, mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 p.Met1Val (c.1A>G) in the general population?

TTC19 p.Met1Val (c.1A>G) is very rare (popmax 0.00578%, nfe) (gnomAD).

TTC19 p.Met1Val

c.1A>G · rs749196122 · VCV488973

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00578%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.472	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.46, phastCons 1
Overall
CADD	19.08	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00578% European (non-Finnish) · 66/1,142,150 alleles

Filtering AF 0.00466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00425%

Overall 0.00447% 68/1,521,030 alleles · very rare exomes 67/1,368,934 · genomes 1/152,096 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00578%	17,305
Remaining individualsnot grpmax-eligible	0.00169%	59,090
South Asian	0.00121%	82,544

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.Met1Val
Coding: c.1A>G
MANE Select: NM_017775
dbSNP: rs749196122
Type: single nucleotide variant
Location: chr17:15999849 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial complex III deficiency nuclear type 2

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.Ala200Val 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-met1val (accessed [today's date]).

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