Is TRAIP p.Arg403Thr (c.1208G>C) pathogenic?

TRAIP p.Arg403Thr (c.1208G>C) is classified Uncertain significance in TRAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). AlphaMissense: likely benign (0.0895); Absent from gnomAD v4.1.

How common is TRAIP p.Arg403Thr (c.1208G>C) in the general population?

TRAIP p.Arg403Thr (c.1208G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAIP p.Arg403Thr (c.1208G>C)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

TRAIP p.Arg403Thr

c.1208G>C · VCV4718614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.97	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 0.49	GERP -3.1, phastCons 0.016
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	8.791	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

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: TRAIP
Protein: p.Arg403Thr
Coding: c.1208G>C
MANE Select: NM_005879
Type: single nucleotide variant
Location: chr3:49829645 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 403: the 'interaction with cyld' region

Full TRAIP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAIP p.Arg436Cys Uncertain significance ★★ ⚠ same type
TRAIP p.Arg436His Uncertain significance ★★ ⚠ same type
TRAIP p.Asp244His Uncertain significance ★★ ⚠ same type
TRAIP p.Asp431Gly Uncertain significance ★★ ⚠ same type
TRAIP p.Gln36Arg Uncertain significance ★★ ⚠ same type
TRAIP p.Glu209Lys Uncertain significance ★★ same type
TRAIP p.Gly421Ser Uncertain significance ★★ ⚠ same type
TRAIP p.Ile104Met 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/traip-p-arg403thr (accessed [today's date]).

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