Is TRAIP p.Lys95Glu (c.283A>G) pathogenic?

TRAIP p.Lys95Glu (c.283A>G) is classified Uncertain significance in TRAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.221); Ultra-rare (popmax 0.0154%, sas); Associated with Inborn genetic diseases.

What condition is associated with TRAIP p.Lys95Glu (c.283A>G)?

TRAIP p.Lys95Glu (c.283A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TRAIP p.Lys95Glu (c.283A>G) in the general population?

TRAIP p.Lys95Glu (c.283A>G) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about TRAIP p.Lys95Glu (c.283A>G)?

AlphaMissense predicts likely benign (score 0.221) — an in-silico prediction, not a clinical call.

TRAIP p.Lys95Glu

c.283A>G · VCV4833621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.221 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.221	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	22.2	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 0.0154% South Asian · 14/90,878 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00737%

Overall 0.00106% 17/1,607,762 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,491
Remaining individualsnot grpmax-eligible	0.00322%	31,068
African / African-American	0.00134%	74,812

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.Lys95Glu
Coding: c.283A>G
MANE Select: NM_005879
Type: single nucleotide variant
Location: chr3:49843926 (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.Glu209Lys Uncertain significance ★★ same condition
TRAIP p.Gly421Ser Uncertain significance ★★ ⚠ same condition
TRAIP p.Ile104Met 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-lys95glu (accessed [today's date]).

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