Is IFT80 p.Ile203Phe (c.607A>T) pathogenic?

IFT80 p.Ile203Phe (c.607A>T) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: ambiguous (0.4759); Very rare (popmax 0.00448%, eas); Associated with Inborn genetic diseases.

What condition is associated with IFT80 p.Ile203Phe (c.607A>T)?

IFT80 p.Ile203Phe (c.607A>T) is associated with Inborn genetic diseases (ClinVar).

How common is IFT80 p.Ile203Phe (c.607A>T) in the general population?

IFT80 p.Ile203Phe (c.607A>T) is very rare (popmax 0.00448%, eas) (gnomAD).

What do computational predictors say about IFT80 p.Ile203Phe (c.607A>T)?

AlphaMissense predicts ambiguous (score 0.4759) — an in-silico prediction, not a clinical call.

IFT80 p.Ile203Phe

c.607A>T · VCV3527967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4759 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4759	ambiguous
REVEL	0.515	indeterminate
SaProt	LLR -14.21	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	27.4	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 0.00448% East Asian · 2/44,672 alleles

Filtering AF 0.000742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000188% 3/1,593,582 alleles · very rare exomes 3/1,441,268 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00448%	22,336
European (non-Finnish)	8.61e-05%	1,161,827

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.Ile203Phe
Coding: c.607A>T
MANE Select: NM_020800
Type: single nucleotide variant
Location: chr3:160357521 (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-ile203phe (accessed [today's date]).

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