Is TRAK1 p.Ser447Phe (c.1340C>T) pathogenic?

TRAK1 p.Ser447Phe (c.1340C>T) is classified Uncertain significance in TRAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: ambiguous (0.4724); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRAK1 p.Ser447Phe (c.1340C>T)?

TRAK1 p.Ser447Phe (c.1340C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRAK1 p.Ser447Phe (c.1340C>T) in the general population?

TRAK1 p.Ser447Phe (c.1340C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAK1 p.Ser447Phe (c.1340C>T)?

AlphaMissense predicts ambiguous (score 0.4724) — an in-silico prediction, not a clinical call.

TRAK1 p.Ser447Phe

c.1340C>T · VCV3460760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4724	ambiguous
REVEL	0.178	moderately benign-leaning
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 111 kb · p 0.024 · regional, not allelic
Overall
CADD	29.1	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.Ser447Phe
Coding: c.1340C>T
MANE Select: NM_001042646
Type: single nucleotide variant
Location: chr3:42200967 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.19
Residue 447: the 'interaction with hgs' region

Full TRAK1 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

TRAK1 p.Ala334Thr Uncertain significance ★★ ⚠ same condition
TRAK1 p.Ala498Val Uncertain significance ★★ ⚠ same condition
TRAK1 p.Ala655Val Uncertain significance ★★ ⚠ same condition
TRAK1 p.Ala861Thr Uncertain significance ★★ ⚠ same condition
TRAK1 p.Arg165Gln Uncertain significance ★★ ⚠ same condition
TRAK1 p.Arg279Cys Uncertain significance ★★ same condition
TRAK1 p.Arg534His Uncertain significance ★★ ⚠ same condition
TRAK1 p.Arg552Cys 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/trak1-p-ser447phe (accessed [today's date]).

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