Is IFT80 p.Arg402Cys (c.1204C>T) pathogenic?

IFT80 p.Arg402Cys (c.1204C>T) is classified Uncertain significance in IFT80 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-02). AlphaMissense: ambiguous (0.4708); Ultra-rare (popmax 0.0255%, afr); Associated with Jeune syndrome.

What condition is associated with IFT80 p.Arg402Cys (c.1204C>T)?

IFT80 p.Arg402Cys (c.1204C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 2 (ClinVar).

How common is IFT80 p.Arg402Cys (c.1204C>T) in the general population?

IFT80 p.Arg402Cys (c.1204C>T) is ultra-rare (popmax 0.0255%, afr) (gnomAD).

What do computational predictors say about IFT80 p.Arg402Cys (c.1204C>T)?

AlphaMissense predicts ambiguous (score 0.4708) — an in-silico prediction, not a clinical call.

IFT80 p.Arg402Cys

c.1204C>T · rs190990464 · VCV1026307

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0255%, afr)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.4708	ambiguous
REVEL	0.38	indeterminate
SaProt	LLR -10.21	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0255% African / African-American · 19/74,642 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00299% 48/1,602,766 alleles · ultra-rare exomes 30/1,450,906 · genomes 18/151,860 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0255%	3,929
Admixed American	0.0219%	4,568
East Asian	0.00897%	11,154
South Asian	0.00557%	17,954
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,442
European (non-Finnish)	0.000512%	195,328

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: IFT80
Protein: p.Arg402Cys
Coding: c.1204C>T
MANE Select: NM_020800
dbSNP: rs190990464
Type: single nucleotide variant
Location: chr3:160300994 (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

Also linked: asphyxiating thoracic dystrophy 2

Similar variants

IFT80 p.Arg402Gly Uncertain significance ★ ⚠ 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 c.*108A>G Uncertain significance ★★ same condition
IFT80 p.Ala154Val 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-arg402cys (accessed [today's date]).

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