Is IFT74 p.Arg288Ter (c.862C>T) pathogenic?

IFT74 p.Arg288Ter (c.862C>T) is classified Likely pathogenic in IFT74 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-02). Very rare (popmax 0.00895%, eas); Associated with IFT74-related disorder.

What condition is associated with IFT74 p.Arg288Ter (c.862C>T)?

IFT74 p.Arg288Ter (c.862C>T) is associated with IFT74-related disorder (ClinVar).

How common is IFT74 p.Arg288Ter (c.862C>T) in the general population?

IFT74 p.Arg288Ter (c.862C>T) is very rare (popmax 0.00895%, eas) (gnomAD).

IFT74 p.Arg288Ter

c.862C>T · VCV3348680

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00895%, eas)

Conditions

IFT74-related disorder

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 11 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.83, phastCons 1
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 0.00895% East Asian · 4/44,714 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000497% 8/1,610,394 alleles · very rare exomes 8/1,458,344 · genomes 0/152,050 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00895%	11,179
South Asian	0.0011%	90,618
European (non-Finnish)	0.000255%	392,662

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: IFT74
Protein: p.Arg288Ter
Coding: c.862C>T
MANE Select: NM_025103
Type: single nucleotide variant
Location: chr9:27016979 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 288: a UniProt-annotated variant site (in jbts40)

Full IFT74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

IFT74-related disorder

Similar variants

IFT74 p.Arg288Gln Uncertain significance ★ ⚠ same residue
IFT74 p.Arg288Leu Uncertain significance ★ ⚠ same residue
IFT74 c.1685-1G>T Pathogenic/Likely pathogenic ★★ same condition
IFT74 p.Thr327Lys Uncertain significance ★★ ⚠ same condition
IFT74 p.Gln342Ter Conflicting classifications of pathogenicity ★ same condition
IFT74 c.1054+7363T>C Uncertain significance same condition
IFT74 c.1054+7400A>C Uncertain significance same condition
IFT74 c.1054+7405G>A 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/ift74-p-arg288ter (accessed [today's date]).

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