Is IFT54 p.Arg565Ter (c.1693C>T) pathogenic?

IFT54 p.Arg565Ter (c.1693C>T) is classified Pathogenic/Likely pathogenic in IFT54 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-07). Very rare (popmax 0.00223%, eas); Associated with Senior-Loken syndrome 9.

What condition is associated with IFT54 p.Arg565Ter (c.1693C>T)?

IFT54 p.Arg565Ter (c.1693C>T) is associated with Senior-Loken syndrome 9 (ClinVar).

How common is IFT54 p.Arg565Ter (c.1693C>T) in the general population?

IFT54 p.Arg565Ter (c.1693C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Senior-Loken syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

IFT54 p.Arg565Ter

c.1693C>T · rs760692076 · VCV1025887

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Senior-Loken syndrome 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -2.4, phastCons 0.99
Overall
CADD	37.0	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 0.00223% East Asian · 1/44,894 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000682% 11/1,612,536 alleles · very rare exomes 9/1,460,362 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,576
East Asiangrpmax	0.00223%	44,894
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000678%	147,470

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg565Ter
Coding: c.1693C>T
MANE Select: NM_015650
dbSNP: rs760692076
Type: single nucleotide variant
Location: chr2:238397462 (GRCh38)
Structure: AlphaFold pLDDT 61.95 · 2 PDB
Residue 565: the 'disc1-interaction domain' region

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

Disease context

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

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

TRAF3IP1 p.Arg565Gln Uncertain significance ★★ ⚠ same residue
IFT54 p.Gly355Glu Uncertain significance ★★ ⚠ same condition
IFT54 p.Pro30Ser Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Arg271Gln Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Arg271Trp Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Arg470Trp Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Glu229Lys Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Thr588Met Uncertain significance ★★ ⚠ 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-arg565ter (accessed [today's date]).

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