Is IFT80 p.Ala701Pro (c.2101G>C) pathogenic?

IFT80 p.Ala701Pro (c.2101G>C) is classified Conflicting classifications of pathogenicity in IFT80 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-12-30). AlphaMissense: likely pathogenic (0.9874); Ultra-rare (popmax 0.0363%, sas); Associated with Jeune syndrome.

What condition is associated with IFT80 p.Ala701Pro (c.2101G>C)?

IFT80 p.Ala701Pro (c.2101G>C) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 2 (ClinVar).

How common is IFT80 p.Ala701Pro (c.2101G>C) in the general population?

IFT80 p.Ala701Pro (c.2101G>C) is ultra-rare (popmax 0.0363%, sas) (gnomAD).

What do computational predictors say about IFT80 p.Ala701Pro (c.2101G>C)?

AlphaMissense predicts likely pathogenic (score 0.9874) — an in-silico prediction, not a clinical call.

IFT80 p.Ala701Pro

c.2101G>C · rs137853116 · VCV991

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9874 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0363%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.9874	likely pathogenic · top 3% in IFT80
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -14.66	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 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	31.0	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 0.0363% South Asian · 33/91,020 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.00223% 36/1,612,852 alleles · ultra-rare exomes 32/1,460,628 · genomes 4/152,224 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0363%	2,758
Remaining individualsnot grpmax-eligible	0.0032%	31,216
European (non-Finnish)	8.48e-05%	1,179,154

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.Ala701Pro
Coding: c.2101G>C
MANE Select: NM_020800
dbSNP: rs137853116
Type: single nucleotide variant
Location: chr3:160268535 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.50
Residue 701: a UniProt-annotated variant site (in srtd2)

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-ala701pro (accessed [today's date]).

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