Is IFT81 p.Ile5Val (c.13A>G) pathogenic?

IFT81 p.Ile5Val (c.13A>G) is classified Uncertain significance in IFT81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: likely benign (0.109); Very rare (popmax 0.00226%, eas); Associated with Inborn genetic diseases.

What condition is associated with IFT81 p.Ile5Val (c.13A>G)?

IFT81 p.Ile5Val (c.13A>G) is associated with Inborn genetic diseases (ClinVar).

How common is IFT81 p.Ile5Val (c.13A>G) in the general population?

IFT81 p.Ile5Val (c.13A>G) is very rare (popmax 0.00226%, eas) (gnomAD).

What do computational predictors say about IFT81 p.Ile5Val (c.13A>G)?

AlphaMissense predicts likely benign (score 0.109) — an in-silico prediction, not a clinical call.

IFT81 p.Ile5Val

c.13A>G · VCV4621985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00226%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.109	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.022 · regional, not allelic
Overall
CADD	19.97	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 0.00226% East Asian · 1/44,160 alleles

Overall 0.00014% 2/1,429,368 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00226%	44,160
European (non-Finnish)	8.56e-05%	1,168,106

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: IFT81
Protein: p.Ile5Val
Coding: c.13A>G
MANE Select: NM_014055
Type: single nucleotide variant
Location: chr12:110127393 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.45
Residue 5: the 'ch (calponin-homology)-like region' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFT81 p.Ala116Ser Uncertain significance ★★ ⚠ same condition
IFT81 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
IFT81 p.Ala254Ser Uncertain significance ★★ ⚠ same condition
IFT81 p.Ala357Gly Uncertain significance ★★ ⚠ same condition
IFT81 p.Arg213Gln Uncertain significance ★★ same condition
IFT81 p.Arg251Gly Uncertain significance ★★ ⚠ same condition
IFT81 p.Arg353His Uncertain significance ★★ ⚠ same condition
IFT81 p.Arg399Leu 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/ift81-p-ile5val (accessed [today's date]).

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