Is TRAIP p.Arg290Ser (c.868C>A) pathogenic?

TRAIP p.Arg290Ser (c.868C>A) is classified Uncertain significance in TRAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-04). AlphaMissense: likely pathogenic (0.7941); Absent from gnomAD v4.1; Associated with Seckel syndrome 9.

What condition is associated with TRAIP p.Arg290Ser (c.868C>A)?

TRAIP p.Arg290Ser (c.868C>A) is associated with Seckel syndrome 9 (ClinVar).

How common is TRAIP p.Arg290Ser (c.868C>A) in the general population?

TRAIP p.Arg290Ser (c.868C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAIP p.Arg290Ser (c.868C>A)?

AlphaMissense predicts likely pathogenic (score 0.7941) — an in-silico prediction, not a clinical call.

TRAIP p.Arg290Ser

c.868C>A · rs201373472 · VCV2437226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Seckel syndrome 9

Computational evidence

Protein change
AlphaMissense	0.7941	likely pathogenic
REVEL	0.29	benign-leaning
SaProt	LLR -4.57	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	27.6	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

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.Arg290Ser
Coding: c.868C>A
MANE Select: NM_005879
dbSNP: rs201373472
Type: single nucleotide variant
Location: chr3:49839788 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 290: the 'interaction with cyld' region

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

Disease context

Seckel syndrome 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAIP p.Arg290Cys Uncertain significance ★ ⚠ same residue
TRAIP p.Arg290His Uncertain significance ★ ⚠ same residue
TRAIP p.Arg436Cys Uncertain significance ★★ ⚠ same condition
TRAIP p.Lys61Arg Uncertain significance ★★ ⚠ same condition
TRAIP p.Ser330Phe Uncertain significance ★★ ⚠ same condition
TRAIP c.240+45G>A Benign ★★ same condition
TRAIP c.99-9T>G Benign/Likely benign ★★ same condition
TRAIP p.Gln101= Benign/Likely benign ★★ 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-arg290ser (accessed [today's date]).

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