Is IFT81 p.Ser39Arg (c.117T>G) pathogenic?

IFT81 p.Ser39Arg (c.117T>G) is classified Uncertain significance in IFT81 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely pathogenic (0.9161); Absent from gnomAD v4.1.

How common is IFT81 p.Ser39Arg (c.117T>G) in the general population?

IFT81 p.Ser39Arg (c.117T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT81 p.Ser39Arg (c.117T>G)?

AlphaMissense predicts likely pathogenic (score 0.9161) — an in-silico prediction, not a clinical call.

IFT81 p.Ser39Arg

c.117T>G · rs2499775590 · VCV1954136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9161 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9161	likely pathogenic · top 2% in IFT81
REVEL	0.401	indeterminate
SaProt	LLR -10.76	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.022 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: IFT81
Protein: p.Ser39Arg
Coding: c.117T>G
MANE Select: NM_014055
dbSNP: rs2499775590
Type: single nucleotide variant
Location: chr12:110127497 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.45
Residue 39: the 'ch (calponin-homology)-like region' region

Full IFT81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFT81 c.1717-2A>G Pathogenic/Likely pathogenic ★★ same type
IFT81 c.249-1G>A Pathogenic/Likely pathogenic ★★ same type
IFT81 p.Arg213Ter Pathogenic/Likely pathogenic ★★ same type
IFT81 p.Arg399Ter Pathogenic/Likely pathogenic ★★ same type
IFT81 p.Arg481Ter Pathogenic/Likely pathogenic ★★ same type
IFT81 p.Arg512Ter Pathogenic/Likely pathogenic ★★ same type
IFT81 p.Arg64Ter Pathogenic ★★ same type
IFT81 p.Leu122Ter Pathogenic/Likely pathogenic ★★ 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/ift81-p-ser39arg (accessed [today's date]).

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