Is TRAF3IP1 p.Ser288Phe (c.863C>T) pathogenic?

TRAF3IP1 p.Ser288Phe (c.863C>T) is classified Uncertain significance in TRAF3IP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-12). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.00424%, afr).

How common is TRAF3IP1 p.Ser288Phe (c.863C>T) in the general population?

TRAF3IP1 p.Ser288Phe (c.863C>T) is very rare (popmax 0.00424%, afr) (gnomAD).

What do computational predictors say about TRAF3IP1 p.Ser288Phe (c.863C>T)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

TRAF3IP1 p.Ser288Phe

c.863C>T · rs950187650 · VCV1966475

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00424%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -9.39	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 0.086	GERP 0.23
Regional constraint	o/e 0.94	unconstrained · MANE · 77 kb · p 0.082 · regional, not allelic
Overall
CADD	15.5	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 0.00424% African / African-American · 3/70,692 alleles

Filtering AF 0.00113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000612%

Overall 0.000543% 8/1,474,428 alleles · very rare exomes 6/1,322,312 · genomes 2/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00424%	23,564
European (non-Finnish)	0.00045%	222,465

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: TRAF3IP1
Protein: p.Ser288Phe
Coding: c.863C>T
MANE Select: NM_015650
dbSNP: rs950187650
Type: single nucleotide variant
Location: chr2:238329290 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.95 · 2 PDB
Residue 288: the 'abolishes microtubules-binding when missing' region; the 'disordered' region; the 'disc1-interaction domain' region

Full TRAF3IP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFT54 c.1159+1G>C Likely pathogenic ★★ same type
IFT54 c.988-1G>A Likely pathogenic ★★ same type
IFT54 c.988-1G>C Likely pathogenic ★★ same type
IFT54 p.Arg565Ter Pathogenic/Likely pathogenic ★★ same type
IFT54 p.Trp572Ter Pathogenic/Likely pathogenic ★★ same type
IFT54 c.1452-5T>G Uncertain significance ★★ same type
IFT54 c.1910+3G>T Uncertain significance ★★ same type
IFT54 p.Ala513Val 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/traf3ip1-p-ser288phe (accessed [today's date]).

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