Is IFT80 p.Trp40Arg (c.118T>A) pathogenic?

IFT80 p.Trp40Arg (c.118T>A) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). AlphaMissense: likely pathogenic (0.9911); Absent from gnomAD v4.1; Associated with Jeune syndrome.

What condition is associated with IFT80 p.Trp40Arg (c.118T>A)?

IFT80 p.Trp40Arg (c.118T>A) is associated with Jeune syndrome (ClinVar).

How common is IFT80 p.Trp40Arg (c.118T>A) in the general population?

IFT80 p.Trp40Arg (c.118T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT80 p.Trp40Arg (c.118T>A)?

AlphaMissense predicts likely pathogenic (score 0.9911) — an in-silico prediction, not a clinical call.

IFT80 p.Trp40Arg

c.118T>A · rs2473512091 · VCV2001469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.9911	likely pathogenic · top 2% in IFT80
REVEL	0.71	pathogenic-leaning
SaProt	LLR -11.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: IFT80
Protein: p.Trp40Arg
Coding: c.118T>A
MANE Select: NM_020800
dbSNP: rs2473512091
Type: single nucleotide variant
Location: chr3:160381644 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.50

Full IFT80 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

IFT80 p.Trp40Ter Pathogenic ★ same residue
IFT80 p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
IFT80 p.Trp155Ter Pathogenic/Likely pathogenic ★★ same condition
IFT80 c.1076+6C>A Uncertain significance ★★ same condition
IFT80 c.1836+5T>C Uncertain significance ★★ same condition
IFT80 c.370+6T>C Uncertain significance ★★ same condition
IFT80 p.Ala154Val Uncertain significance ★★ ⚠ same condition
IFT80 p.Ala236Val 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/ift80-p-trp40arg (accessed [today's date]).

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