Is TTC19 p.Ala89Thr (c.265G>A) pathogenic?

TTC19 p.Ala89Thr (c.265G>A) is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely benign (0.0805); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Ala89Thr (c.265G>A)?

TTC19 p.Ala89Thr (c.265G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TTC19 p.Ala89Thr (c.265G>A) in the general population?

TTC19 p.Ala89Thr (c.265G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about TTC19 p.Ala89Thr (c.265G>A)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

TTC19 p.Ala89Thr

c.265G>A · VCV3463214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -10.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.81, phastCons 0.13
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	15.52	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 0.004% African / African-American · 3/74,952 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000314% 5/1,594,530 alleles · very rare exomes 5/1,442,194 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,984
Remaining individualsnot grpmax-eligible	0.00161%	62,044
European (non-Finnish)	8.48e-05%	1,178,892

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.Ala89Thr
Coding: c.265G>A
MANE Select: NM_017775
Type: single nucleotide variant
Location: chr17:16000198 (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-ala89thr (accessed [today's date]).

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