Is IFT88 p.Pro9Ser (c.25C>T) pathogenic?

IFT88 p.Pro9Ser (c.25C>T) is classified Uncertain significance in IFT88 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely benign (0.1181); Very rare (popmax 0.00586%, nfe).

How common is IFT88 p.Pro9Ser (c.25C>T) in the general population?

IFT88 p.Pro9Ser (c.25C>T) is very rare (popmax 0.00586%, nfe) (gnomAD).

What do computational predictors say about IFT88 p.Pro9Ser (c.25C>T)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

IFT88 p.Pro9Ser

c.25C>T · rs200359008 · VCV2522041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00586%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 117 kb · p 0.59 · regional, not allelic
Overall
CADD	22.8	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 0.00586% European (non-Finnish) · 69/1,178,400 alleles

Filtering AF 0.00471% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00447% 72/1,611,350 alleles · very rare exomes 71/1,459,192 · genomes 1/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00586%	17,078
Remaining individualsnot grpmax-eligible	0.00481%	20,801

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.Pro9Ser
Coding: c.25C>T
MANE Select: NM_006531
dbSNP: rs200359008
Type: single nucleotide variant
Location: chr13:20574410 (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.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
IFT88 p.Arg369His Uncertain significance ★★ ⚠ same type
IFT88 p.Arg533Trp 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-pro9ser (accessed [today's date]).

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