Is IFT80 p.Pro239Ser (c.715C>T) pathogenic?

IFT80 p.Pro239Ser (c.715C>T) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: likely benign (0.0954); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IFT80 p.Pro239Ser (c.715C>T)?

IFT80 p.Pro239Ser (c.715C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IFT80 p.Pro239Ser (c.715C>T) in the general population?

IFT80 p.Pro239Ser (c.715C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about IFT80 p.Pro239Ser (c.715C>T)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

IFT80 p.Pro239Ser

c.715C>T · rs2473420309 · VCV2304524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.426	indeterminate
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	24.0	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 0.000339% European (non-Finnish) · 4/1,179,990 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,128 alleles · very rare exomes 4/1,461,820 · genomes 0/152,308 · joint denominator

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.Pro239Ser
Coding: c.715C>T
MANE Select: NM_020800
dbSNP: rs2473420309
Type: single nucleotide variant
Location: chr3:160356075 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFT80 p.Ala154Val Uncertain significance ★★ ⚠ same condition
IFT80 p.Arg316Gly Uncertain significance ★★ ⚠ same condition
IFT80 p.Glu499Lys Uncertain significance ★★ ⚠ same condition
IFT80 p.Gly727Ser Uncertain significance ★★ ⚠ same condition
IFT80 p.His90Arg Uncertain significance ★★ same condition
IFT80 p.Ile132Leu Uncertain significance ★★ same condition
IFT80 p.Ile172Asn Uncertain significance ★★ ⚠ same condition
IFT80 p.Ile279Val 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-pro239ser (accessed [today's date]).

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