Is IFT80 p.Pro777Ser (c.2329C>T) pathogenic?

IFT80 p.Pro777Ser (c.2329C>T) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely benign (0.0644); Absent from gnomAD v4.1; Associated with Jeune syndrome.

What condition is associated with IFT80 p.Pro777Ser (c.2329C>T)?

IFT80 p.Pro777Ser (c.2329C>T) is associated with Jeune syndrome (ClinVar).

How common is IFT80 p.Pro777Ser (c.2329C>T) in the general population?

IFT80 p.Pro777Ser (c.2329C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT80 p.Pro777Ser (c.2329C>T)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

IFT80 p.Pro777Ser

c.2329C>T · rs1387613728 · VCV2015424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -4.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	15.12	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Pro777Ser
Coding: c.2329C>T
MANE Select: NM_020800
dbSNP: rs1387613728
Type: single nucleotide variant
Location: chr3:160258530 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.50
Residue 777: the 'disordered' region

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.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
IFT80 p.Arg220Cys 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-pro777ser (accessed [today's date]).

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