Is IFT80 p.Pro267Ser (c.799C>T) pathogenic?

IFT80 p.Pro267Ser (c.799C>T) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: ambiguous (0.5203); Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with IFT80 p.Pro267Ser (c.799C>T)?

IFT80 p.Pro267Ser (c.799C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IFT80 p.Pro267Ser (c.799C>T) in the general population?

IFT80 p.Pro267Ser (c.799C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about IFT80 p.Pro267Ser (c.799C>T)?

AlphaMissense predicts ambiguous (score 0.5203) — an in-silico prediction, not a clinical call.

IFT80 p.Pro267Ser

c.799C>T · rs745579749 · VCV3108466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5203 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5203	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -12.01	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense 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	26.2	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 0.0134% East Asian · 6/44,820 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,611,338 alleles · ultra-rare exomes 6/1,459,448 · genomes 0/151,890 · 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.Pro267Ser
Coding: c.799C>T
MANE Select: NM_020800
dbSNP: rs745579749
Type: single nucleotide variant
Location: chr3:160319918 (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-pro267ser (accessed [today's date]).

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