Is IFT54 p.Arg348Ter (c.1042C>T) pathogenic?

IFT54 p.Arg348Ter (c.1042C>T) is classified Likely pathogenic in IFT54 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). Very rare (popmax 0.0011%, sas); Associated with TRAF3IP1-related disorder.

What condition is associated with IFT54 p.Arg348Ter (c.1042C>T)?

IFT54 p.Arg348Ter (c.1042C>T) is associated with TRAF3IP1-related disorder (ClinVar).

How common is IFT54 p.Arg348Ter (c.1042C>T) in the general population?

IFT54 p.Arg348Ter (c.1042C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

IFT54 p.Arg348Ter

c.1042C>T · VCV4960783

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

TRAF3IP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 17
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.73	GERP 1.2, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,550 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,610,480 alleles · very rare exomes 4/1,458,758 · genomes 0/151,722 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,550
European (non-Finnish)	0.000255%	392,762

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: IFT54
Protein: p.Arg348Ter
Coding: c.1042C>T
MANE Select: NM_015650
Type: single nucleotide variant
Location: chr2:238334014 (GRCh38)
Structure: AlphaFold pLDDT 61.95 · 2 PDB
Residue 348: the 'disordered' region; the 'disc1-interaction domain' region

Full IFT54 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TRAF3IP1-related disorder

Similar variants

TRAF3IP1 p.Arg348Leu Uncertain significance ★★ ⚠ same residue
TRAF3IP1 p.Arg348Gln Uncertain significance ★ ⚠ same residue
TRAF3IP1 p.Arg348= Likely benign ★ same residue
IFT54 c.1159+1G>C Likely pathogenic ★★ same condition
IFT54 c.988-1G>A Likely pathogenic ★★ same condition
IFT54 c.988-1G>C Likely pathogenic ★★ same condition
IFT54 p.Trp572Ter Pathogenic/Likely pathogenic ★★ same condition
IFT54 p.Arg182Ter Likely pathogenic ★ 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/ift54-p-arg348ter (accessed [today's date]).

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