Is IFT74 p.Ser95Pro (c.283T>C) pathogenic?

IFT74 p.Ser95Pro (c.283T>C) is classified Uncertain significance in IFT74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). AlphaMissense: ambiguous (0.5251); Absent from gnomAD v4.1.

How common is IFT74 p.Ser95Pro (c.283T>C) in the general population?

IFT74 p.Ser95Pro (c.283T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT74 p.Ser95Pro (c.283T>C)?

AlphaMissense predicts ambiguous (score 0.5251) — an in-silico prediction, not a clinical call.

IFT74 p.Ser95Pro

c.283T>C · rs2489317568 · VCV2002444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5251	ambiguous
REVEL	0.188	benign-leaning
SaProt	LLR -11.51	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.3, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	27.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IFT74
Protein: p.Ser95Pro
Coding: c.283T>C
MANE Select: NM_025103
dbSNP: rs2489317568
Type: single nucleotide variant
Location: chr9:26980597 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 95: a UniProt-annotated variant site (in jbts40)

Full IFT74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFT74 c.1685-1G>T Pathogenic/Likely pathogenic ★★ same type
IFT74 p.Gln179Glu Pathogenic/Likely pathogenic ★★ ⚠ same type
IFT74 p.Glu120Ter Pathogenic/Likely pathogenic ★★ same type
IFT74 p.Glu285Ter Pathogenic/Likely pathogenic ★★ same type
IFT74 p.Ala196Val Uncertain significance ★★ ⚠ same type
IFT74 p.Ala558Val Uncertain significance ★★ ⚠ same type
IFT74 p.Arg182Gln Uncertain significance ★★ ⚠ same type
IFT74 p.Arg402Gly 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/ift74-p-ser95pro (accessed [today's date]).

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