Is TRAK1 p.Pro877Ser (c.2629C>T) pathogenic?

TRAK1 p.Pro877Ser (c.2629C>T) is classified Uncertain significance in TRAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely benign (0.0637); Very rare (popmax 0.00167%, amr).

How common is TRAK1 p.Pro877Ser (c.2629C>T) in the general population?

TRAK1 p.Pro877Ser (c.2629C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about TRAK1 p.Pro877Ser (c.2629C>T)?

AlphaMissense predicts likely benign (score 0.0637) — an in-silico prediction, not a clinical call.

TRAK1 p.Pro877Ser

c.2629C>T · rs748881731 · VCV1482374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0637	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.55	GERP -0.61, phastCons 0.002
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.07 · regional, not allelic
Overall
CADD	15.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,028 alleles

Overall 0.000186% 3/1,613,548 alleles · very rare exomes 3/1,461,246 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,028
South Asian	0.0011%	91,072
European (non-Finnish)	8.48e-05%	1,179,898

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.Pro877Ser
Coding: c.2629C>T
MANE Select: NM_001042646
dbSNP: rs748881731
Type: single nucleotide variant
Location: chr3:42223504 (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-pro877ser (accessed [today's date]).

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