Is TRAK1 p.Ser503Phe (c.1508C>T) pathogenic?

TRAK1 p.Ser503Phe (c.1508C>T) is classified Uncertain significance in TRAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely pathogenic (0.6447); Absent from gnomAD v4.1.

How common is TRAK1 p.Ser503Phe (c.1508C>T) in the general population?

TRAK1 p.Ser503Phe (c.1508C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAK1 p.Ser503Phe (c.1508C>T)?

AlphaMissense predicts likely pathogenic (score 0.6447) — an in-silico prediction, not a clinical call.

TRAK1 p.Ser503Phe

c.1508C>T · VCV3364749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6447 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6447	likely pathogenic
REVEL	0.287	benign-leaning
SaProt	LLR -13.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 111 kb · p 0.024 · regional, not allelic
Overall
CADD	29.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRAK1
Protein: p.Ser503Phe
Coding: c.1508C>T
MANE Select: NM_001042646
Type: single nucleotide variant
Location: chr3:42202516 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.19
Residue 503: the 'interaction with hgs' region

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

Similar variants

TRAK1 c.1963+258C>T Uncertain significance ★★ same type
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
TRAK1 p.Arg117Gln Uncertain significance ★★ ⚠ same type
TRAK1 p.Arg165Gln Uncertain significance ★★ ⚠ same type
TRAK1 p.Arg279Cys 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-ser503phe (accessed [today's date]).

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