Is TRAIP p.Glu209Lys (c.625G>A) pathogenic?

TRAIP p.Glu209Lys (c.625G>A) is classified Uncertain significance in TRAIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-23). AlphaMissense: ambiguous (0.4555); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with TRAIP p.Glu209Lys (c.625G>A)?

TRAIP p.Glu209Lys (c.625G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRAIP p.Glu209Lys (c.625G>A) in the general population?

TRAIP p.Glu209Lys (c.625G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TRAIP p.Glu209Lys (c.625G>A)?

AlphaMissense predicts ambiguous (score 0.4555) — an in-silico prediction, not a clinical call.

TRAIP p.Glu209Lys

c.625G>A · rs756300840 · VCV1910040

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4555 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4555	ambiguous
REVEL	0.336	indeterminate
SaProt	LLR -6.23	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	29.7	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00223% 36/1,614,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.012%	8,336
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asian	0.00446%	22,443
South Asian	0.00329%	30,363
Admixed American	0.00167%	60,024
European (non-Finnish)	0.00127%	78,665

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: TRAIP
Protein: p.Glu209Lys
Coding: c.625G>A
MANE Select: NM_005879
dbSNP: rs756300840
Type: single nucleotide variant
Location: chr3:49841065 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB

Full TRAIP 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

TRAIP p.Arg436Cys Uncertain significance ★★ ⚠ same condition
TRAIP p.Arg436His Uncertain significance ★★ ⚠ same condition
TRAIP p.Asp244His Uncertain significance ★★ ⚠ same condition
TRAIP p.Asp431Gly Uncertain significance ★★ ⚠ same condition
TRAIP p.Gln36Arg Uncertain significance ★★ ⚠ same condition
TRAIP p.Gly421Ser Uncertain significance ★★ ⚠ same condition
TRAIP p.Ile104Met Uncertain significance ★★ ⚠ same condition
TRAIP p.Leu340Phe 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/traip-p-glu209lys (accessed [today's date]).

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