Is IFT80 p.Pro407Ser (c.1219C>T) pathogenic?

IFT80 p.Pro407Ser (c.1219C>T) is classified Uncertain significance in IFT80 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.7469); Very rare (popmax 0.00224%, eas); Associated with Jeune syndrome.

What condition is associated with IFT80 p.Pro407Ser (c.1219C>T)?

IFT80 p.Pro407Ser (c.1219C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 2 (ClinVar).

How common is IFT80 p.Pro407Ser (c.1219C>T) in the general population?

IFT80 p.Pro407Ser (c.1219C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about IFT80 p.Pro407Ser (c.1219C>T)?

AlphaMissense predicts likely pathogenic (score 0.7469) — an in-silico prediction, not a clinical call.

IFT80 p.Pro407Ser

c.1219C>T · rs1345262813 · VCV1062392

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.7469	likely pathogenic
REVEL	0.513	indeterminate
SaProt	LLR -11.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.00224% East Asian · 1/44,656 alleles

Overall 0.000187% 3/1,608,554 alleles · very rare exomes 2/1,456,678 · genomes 1/151,876 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,146
East Asiangrpmax	0.00224%	44,656

Remaining individuals 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: IFT80
Protein: p.Pro407Ser
Coding: c.1219C>T
MANE Select: NM_020800
dbSNP: rs1345262813
Type: single nucleotide variant
Location: chr3:160300979 (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.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
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-pro407ser (accessed [today's date]).

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