Is TTC19 p.Ala190Thr (c.568G>A) pathogenic?

TTC19 p.Ala190Thr (c.568G>A) is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: ambiguous (0.4109); Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Ala190Thr (c.568G>A)?

TTC19 p.Ala190Thr (c.568G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TTC19 p.Ala190Thr (c.568G>A) in the general population?

TTC19 p.Ala190Thr (c.568G>A) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about TTC19 p.Ala190Thr (c.568G>A)?

AlphaMissense predicts ambiguous (score 0.4109) — an in-silico prediction, not a clinical call.

TTC19 p.Ala190Thr

c.568G>A · VCV3975250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4109 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4109	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -10.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	29.4	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 0.0187% African / African-American · 14/74,936 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00105% 17/1,614,092 alleles · ultra-rare exomes 6/1,461,856 · genomes 11/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,353
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	8.47e-05%	1,180,025

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.Ala190Thr
Coding: c.568G>A
MANE Select: NM_017775
Type: single nucleotide variant
Location: chr17:16004249 (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

Similar variants

TTC19 p.Ala200Val Uncertain significance ★★ ⚠ same condition
TTC19 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
TTC19 p.Ala85Val Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg102Gly Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg124His Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg294Cys Uncertain significance ★★ ⚠ same condition
TTC19 p.Ile206Met Uncertain significance ★★ ⚠ same condition
TTC19 p.Lys160Gln 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-ala190thr (accessed [today's date]).

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