Is IFT88 p.Ser45Arg (c.135T>G) pathogenic?

IFT88 p.Ser45Arg (c.135T>G) is classified Uncertain significance in IFT88 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9594); Very rare (popmax 0.000424%, nfe).

How common is IFT88 p.Ser45Arg (c.135T>G) in the general population?

IFT88 p.Ser45Arg (c.135T>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about IFT88 p.Ser45Arg (c.135T>G)?

AlphaMissense predicts likely pathogenic (score 0.9594) — an in-silico prediction, not a clinical call.

IFT88 p.Ser45Arg

c.135T>G · rs1566073024 · VCV3009328

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9594 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9594	likely pathogenic · top 4% in IFT88
REVEL	0.21	benign-leaning
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 117 kb · p 0.59 · regional, not allelic
Overall
CADD	20.2	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 0.000424% European (non-Finnish) · 5/1,178,588 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,611,076 alleles · very rare exomes 5/1,458,750 · genomes 0/152,326 · 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: IFT88
Protein: p.Ser45Arg
Coding: c.135T>G
MANE Select: NM_006531
dbSNP: rs1566073024
Type: single nucleotide variant
Location: chr13:20583001 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 77.20

Full IFT88 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFT88 p.Ser45Ile Uncertain significance ★ ⚠ same residue
IFT88 p.Ser45= Likely benign ★ same residue
IFT88 p.Ala327Thr Uncertain significance ★★ ⚠ same type
IFT88 p.Ala37Gly Uncertain significance ★★ ⚠ same type
IFT88 p.Ala458Val Uncertain significance ★★ ⚠ same type
IFT88 p.Ala510Pro Uncertain significance ★★ ⚠ same type
IFT88 p.Ala546Thr Uncertain significance ★★ ⚠ same type
IFT88 p.Ala628Ser Uncertain significance ★★ ⚠ same type

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/ift88-p-ser45arg (accessed [today's date]).

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