Is IFT74 p.Ile28Val (c.82A>G) pathogenic?

IFT74 p.Ile28Val (c.82A>G) is classified Uncertain significance in IFT74 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.0767); Very rare (popmax 0.00314%, nfe).

How common is IFT74 p.Ile28Val (c.82A>G) in the general population?

IFT74 p.Ile28Val (c.82A>G) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about IFT74 p.Ile28Val (c.82A>G)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

IFT74 p.Ile28Val

c.82A>G · VCV4355531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.72	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 1	GERP -0.97, phastCons 0.99
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	7.26	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 0.00314% European (non-Finnish) · 37/1,180,036 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00235% 38/1,614,086 alleles · very rare exomes 37/1,461,874 · genomes 1/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,893
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: IFT74
Protein: p.Ile28Val
Coding: c.82A>G
MANE Select: NM_025103
Type: single nucleotide variant
Location: chr9:26962049 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 28: the 'basic region' region; the 'disordered' region

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-ile28val (accessed [today's date]).

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