Is TRAIP p.Gln428His (c.1284G>T) pathogenic?

TRAIP p.Gln428His (c.1284G>T) is classified Uncertain significance in TRAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: ambiguous (0.3881); Ultra-rare (popmax 0.0947%, nfe).

How common is TRAIP p.Gln428His (c.1284G>T) in the general population?

TRAIP p.Gln428His (c.1284G>T) is ultra-rare (popmax 0.0947%, nfe) (gnomAD).

What do computational predictors say about TRAIP p.Gln428His (c.1284G>T)?

AlphaMissense predicts ambiguous (score 0.3881) — an in-silico prediction, not a clinical call.

TRAIP p.Gln428His

c.1284G>T · rs146306196 · VCV2050540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0947%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3881	ambiguous
REVEL	0.245	benign-leaning
SaProt	LLR -6.48	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -1.1, phastCons 0.98
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	21.3	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 0.0947% European (non-Finnish) · 1,118/1,180,006 alleles

Filtering AF 0.0901% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0883%

Overall 0.0738% 1,191/1,613,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0947%	1,055
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Finnishnot grpmax-eligible	0.0219%	4,572
African / African-American	0.0174%	5,762
Admixed American	0.00667%	14,998

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.Gln428His
Coding: c.1284G>T
MANE Select: NM_005879
dbSNP: rs146306196
Type: single nucleotide variant
Location: chr3:49829461 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 428: 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-gln428his (accessed [today's date]).

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