Is IFT54 p.Pro30Ser (c.88C>T) pathogenic?

IFT54 p.Pro30Ser (c.88C>T) is classified Uncertain significance in IFT54 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-23). AlphaMissense: likely pathogenic (0.9945); Ultra-rare (popmax 0.012%, amr); Associated with Senior-Loken syndrome 9.

What condition is associated with IFT54 p.Pro30Ser (c.88C>T)?

IFT54 p.Pro30Ser (c.88C>T) is associated with Senior-Loken syndrome 9 (ClinVar).

How common is IFT54 p.Pro30Ser (c.88C>T) in the general population?

IFT54 p.Pro30Ser (c.88C>T) is ultra-rare (popmax 0.012%, amr) (gnomAD).

How is Senior-Loken syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IFT54 p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely pathogenic (score 0.9945) — an in-silico prediction, not a clinical call.

IFT54 p.Pro30Ser

c.88C>T · rs1256966921 · VCV951276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9945 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Senior-Loken syndrome 9

Computational evidence

Protein change
AlphaMissense	0.9945	likely pathogenic · top 2% in IFT54
REVEL	0.401	indeterminate
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.47, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 77 kb · p 0.082 · regional, not allelic
Overall
CADD	25.7	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 0.012% Admixed American · 5/41,644 alleles

Filtering AF 0.00472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00304%

Overall 0.000486% 7/1,440,326 alleles · ultra-rare exomes 7/1,288,988 · genomes 0/151,338 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.012%	8,329
European (non-Finnish)	0.000184%	542,199

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: IFT54
Protein: p.Pro30Ser
Coding: c.88C>T
MANE Select: NM_015650
dbSNP: rs1256966921
Type: single nucleotide variant
Location: chr2:238320750 (GRCh38)
Structure: AlphaFold pLDDT 61.95 · 2 PDB
Residue 30: the 'abolishes microtubules-binding when missing' region

Full IFT54 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Senior-Loken syndrome 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

TRAF3IP1 p.Pro30Leu Uncertain significance ★ ⚠ same residue
TRAF3IP1 p.Pro30= Likely benign ★ same residue
IFT54 p.Arg565Ter Pathogenic/Likely pathogenic ★★ same condition
IFT54 p.Gly355Glu Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Arg271Gln Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Arg271Trp Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Arg470Trp Uncertain significance ★★ ⚠ same condition
TRAF3IP1 p.Glu229Lys 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/ift54-p-pro30ser (accessed [today's date]).

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