Is TRAK1 p.Val686Phe (c.2056G>T) pathogenic?

TRAK1 p.Val686Phe (c.2056G>T) is classified Likely benign in TRAK1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.7109); Rare (popmax 0.171%, amr).

How common is TRAK1 p.Val686Phe (c.2056G>T) in the general population?

TRAK1 p.Val686Phe (c.2056G>T) is rare (popmax 0.171%, amr) (gnomAD).

What do computational predictors say about TRAK1 p.Val686Phe (c.2056G>T)?

AlphaMissense predicts likely pathogenic (score 0.7109) — an in-silico prediction, not a clinical call.

TRAK1 p.Val686Phe

c.2056G>T · rs200620651 · VCV1594964

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7109 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.171%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7109	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.07 · regional, not allelic
Overall
CADD	24.9	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 0.171% Admixed American · 101/59,046 alleles

Filtering AF 0.144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.00656% 104/1,585,782 alleles · rare exomes 96/1,434,786 · genomes 8/150,996 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.171%	585
Remaining individualsnot grpmax-eligible	0.0033%	30,275
Finnishnot grpmax-eligible	0.00166%	60,082

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.Val686Phe
Coding: c.2056G>T
MANE Select: NM_001042646
dbSNP: rs200620651
Type: single nucleotide variant
Location: chr3:42219586 (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

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-val686phe (accessed [today's date]).

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