Is IFT80 p.Ser359Phe (c.1076C>T) pathogenic?

IFT80 p.Ser359Phe (c.1076C>T) is classified Benign in IFT80 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). AlphaMissense: ambiguous (0.5263); Low-frequency (popmax 3.78%, amr); Associated with connective tissue disorder.

What condition is associated with IFT80 p.Ser359Phe (c.1076C>T)?

IFT80 p.Ser359Phe (c.1076C>T) is associated with connective tissue disorder, asphyxiating thoracic dystrophy 2, Jeune syndrome (ClinVar).

How common is IFT80 p.Ser359Phe (c.1076C>T) in the general population?

IFT80 p.Ser359Phe (c.1076C>T) is low-frequency (popmax 3.78%, amr) (gnomAD).

What do computational predictors say about IFT80 p.Ser359Phe (c.1076C>T)?

AlphaMissense predicts ambiguous (score 0.5263) — an in-silico prediction, not a clinical call.

IFT80 p.Ser359Phe

c.1076C>T · rs144099135 · VCV193733

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.5263 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.78%, amr)

Conditions

connective tissue disorder

Computational evidence

Protein change
AlphaMissense	0.5263	ambiguous
REVEL	0.451	indeterminate
SaProt	LLR -11.37	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	34.0	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 3.78% Admixed American · 2,259/59,784 alleles

Filtering AF 3.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.6%

Overall 0.809% 11,690/1,445,354 alleles · low-frequency exomes 10,527/1,293,104 · genomes 1,163/152,250 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.51%	22
Admixed Americangrpmax	3.78%	26
Remaining individualsnot grpmax-eligible	0.807%	124
European (non-Finnish)	0.77%	130
Finnishnot grpmax-eligible	0.539%	186
South Asian	0.439%	228
African / African-American	0.333%	300
Middle Eastern	0.129%	775
East Asian	0.118%	848
Ashkenazi Jewishnot grpmax-eligible	0.014%	7,164

Amish 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.Ser359Phe
Coding: c.1076C>T
MANE Select: NM_020800
dbSNP: rs144099135
Type: single nucleotide variant
Location: chr3:160307663 (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

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: asphyxiating thoracic dystrophy 2 Jeune syndrome

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-ser359phe (accessed [today's date]).

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