Is TRAIP p.Arg423Gln (c.1268G>A) pathogenic?

TRAIP p.Arg423Gln (c.1268G>A) is classified Uncertain significance in TRAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). AlphaMissense: likely benign (0.1518); Very rare (popmax 0.00401%, afr).

How common is TRAIP p.Arg423Gln (c.1268G>A) in the general population?

TRAIP p.Arg423Gln (c.1268G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about TRAIP p.Arg423Gln (c.1268G>A)?

AlphaMissense predicts likely benign (score 0.1518) — an in-silico prediction, not a clinical call.

TRAIP p.Arg423Gln

c.1268G>A · rs142854364 · VCV1943576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1518 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1518	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -4.42	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	33.0	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 0.00401% African / African-American · 3/74,904 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00143% 23/1,613,994 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,968
South Asian	0.0022%	45,539
Admixed American	0.00167%	60,004
European (non-Finnish)	0.00144%	69,413

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.Arg423Gln
Coding: c.1268G>A
MANE Select: NM_005879
dbSNP: rs142854364
Type: single nucleotide variant
Location: chr3:49829477 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 423: the 'interaction with cyld' region

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

Similar variants

TRAIP p.Arg423= Benign ★ same residue
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

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-arg423gln (accessed [today's date]).

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