Is TRAK1 p.Ser583= (c.1749C>T) pathogenic?

TRAK1 p.Ser583= (c.1749C>T) is classified Benign in TRAK1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 62.7%, amr) — too common for a highly-penetrant pathogenic allele; Associated with developmental and epileptic encephalopathy, 68.

What condition is associated with TRAK1 p.Ser583= (c.1749C>T)?

TRAK1 p.Ser583= (c.1749C>T) is associated with developmental and epileptic encephalopathy, 68 (ClinVar).

TRAK1 p.Ser583=

Q: How common is TRAK1 p.Ser583= (c.1749C>T) in the general population?

TRAK1 p.Ser583= (c.1749C>T) is common (popmax 62.7%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1749C>T · rs2290134 · VCV1342259

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 62.7%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

developmental and epileptic encephalopathy, 68

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.18	GERP -4.3, phastCons 0.43
Overall
CADD	6.865	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 62.7% Admixed American · 37,611/60,000 alleles

Filtering AF 62.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 61.9%

Overall 51% 822,356/1,612,310 alleles · common exomes 746,196/1,460,426 · genomes 76,160/151,884 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	62.7%	2
Middle Eastern	56.5%	2
South Asian	55.3%	2
Remaining individualsnot grpmax-eligible	51.9%	2
Ashkenazi Jewishnot grpmax-eligible	51.5%	2
European (non-Finnish)	50.5%	2
East Asian	49.9%	2
Finnishnot grpmax-eligible	48.7%	2
African / African-American	46.3%	2
Amishnot grpmax-eligible	40.2%	2

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.Ser583=
Coding: c.1749C>T
MANE Select: NM_001042646
dbSNP: rs2290134
Type: single nucleotide variant
Location: chr3:42209771 (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

developmental and epileptic encephalopathy, 68 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAK1 p.Glu307Gly Uncertain significance ★★ ⚠ same condition
TRAK1 p.Glu621Lys Uncertain significance ★★ ⚠ same condition
TRAK1 p.His71Arg Uncertain significance ★★ ⚠ same condition
TRAK1 p.Leu329Pro Uncertain significance ★★ ⚠ same condition
TRAK1 p.Pro782Leu Uncertain significance ★★ ⚠ same condition
TRAK1 p.Thr497Met Uncertain significance ★★ ⚠ same condition
TRAK1 p.Val190Ile Uncertain significance ★★ ⚠ same condition
TRAK1 c.1744+77G>A Benign ★★ 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/trak1-p-ser583 (accessed [today's date]).

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