Is TRAK1 p.Pro773= (c.2319C>T) pathogenic?

TRAK1 p.Pro773= (c.2319C>T) is classified Likely benign in TRAK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-22). Ultra-rare (popmax 0.0147%, afr); Associated with TRAK1-related disorder.

What condition is associated with TRAK1 p.Pro773= (c.2319C>T)?

TRAK1 p.Pro773= (c.2319C>T) is associated with TRAK1-related disorder (ClinVar).

How common is TRAK1 p.Pro773= (c.2319C>T) in the general population?

TRAK1 p.Pro773= (c.2319C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

TRAK1 p.Pro773=

c.2319C>T · VCV3357027

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

TRAK1-related disorder

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 -0.14	GERP -0.14, phastCons 0.48
Overall
CADD	4.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,932 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000743% 12/1,614,068 alleles · ultra-rare exomes 3/1,461,870 · genomes 9/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,812
European (non-Finnish)	8.47e-05%	1,180,036

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: TRAK1
Protein: p.Pro773=
Coding: c.2319C>T
MANE Select: NM_001042646
Type: single nucleotide variant
Location: chr3:42223194 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.19

Full TRAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TRAK1-related disorder

Similar variants

TRAK1 c.1963+258C>T Uncertain significance ★★ same condition
TRAK1 c.1744+75G>A Uncertain significance same condition
TRAK1 p.Thr444Ser Uncertain significance ⚠ same condition
TRAK1 c.1190+4C>T Likely benign same condition
TRAK1 p.Ala334Thr Uncertain significance ★★ ⚠ same type
TRAK1 p.Ala498Val Uncertain significance ★★ ⚠ same type
TRAK1 p.Ala655Val Uncertain significance ★★ ⚠ same type
TRAK1 p.Ala861Thr Uncertain significance ★★ ⚠ same type

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/trak1-p-pro773 (accessed [today's date]).

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