Is IFT80 p.Ala236Val (c.707C>T) pathogenic?

IFT80 p.Ala236Val (c.707C>T) is classified Uncertain significance in IFT80 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-14). AlphaMissense: likely benign (0.1847); Very rare (popmax 0.00167%, amr); Associated with Jeune syndrome.

What condition is associated with IFT80 p.Ala236Val (c.707C>T)?

IFT80 p.Ala236Val (c.707C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 2 (ClinVar).

How common is IFT80 p.Ala236Val (c.707C>T) in the general population?

IFT80 p.Ala236Val (c.707C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about IFT80 p.Ala236Val (c.707C>T)?

AlphaMissense predicts likely benign (score 0.1847) — an in-silico prediction, not a clinical call.

IFT80 p.Ala236Val

c.707C>T · rs774857269 · VCV343977

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.1847	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00502% 81/1,614,008 alleles · very rare exomes 68/1,461,780 · genomes 13/152,228 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.216%	462
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Admixed Americangrpmax	0.00167%	60,008
European (non-Finnish)	0.000678%	147,497

Ashkenazi Jewish 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.Ala236Val
Coding: c.707C>T
MANE Select: NM_020800
dbSNP: rs774857269
Type: single nucleotide variant
Location: chr3:160356083 (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.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-ala236val (accessed [today's date]).

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