Is IFT74 p.Ile265Val (c.793A>G) pathogenic?

IFT74 p.Ile265Val (c.793A>G) is classified Uncertain significance in IFT74 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-07). AlphaMissense: likely benign (0.1071); Ultra-rare (popmax 0.0323%, afr); Associated with Inborn genetic diseases.

What condition is associated with IFT74 p.Ile265Val (c.793A>G)?

IFT74 p.Ile265Val (c.793A>G) is associated with Inborn genetic diseases (ClinVar).

How common is IFT74 p.Ile265Val (c.793A>G) in the general population?

IFT74 p.Ile265Val (c.793A>G) is ultra-rare (popmax 0.0323%, afr) (gnomAD).

What do computational predictors say about IFT74 p.Ile265Val (c.793A>G)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

IFT74 p.Ile265Val

c.793A>G · rs370062629 · VCV1522209

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0323%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.64	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 5	GERP -0.96, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	15.32	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 0.0323% African / African-American · 24/74,246 alleles

Filtering AF 0.0222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.00163% 26/1,595,326 alleles · ultra-rare exomes 12/1,443,012 · genomes 14/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0323%	3,094
Remaining individualsnot grpmax-eligible	0.00162%	61,634
European (non-Finnish)	8.52e-05%	1,173,778

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.Ile265Val
Coding: c.793A>G
MANE Select: NM_025103
dbSNP: rs370062629
Type: single nucleotide variant
Location: chr9:27016910 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 265: a UniProt-annotated variant site (in jbts40)

Full IFT74 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

IFT74 p.Ile265Arg Uncertain significance ★ ⚠ same residue
IFT74 p.Gln179Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
IFT74 p.Arg182Gln Uncertain significance ★★ ⚠ same condition
IFT74 p.Arg402Gly Uncertain significance ★★ ⚠ same condition
IFT74 p.Arg406His Uncertain significance ★★ ⚠ same condition
IFT74 p.Arg448Cys Uncertain significance ★★ ⚠ same condition
IFT74 p.Arg51Cys Uncertain significance ★★ ⚠ same condition
IFT74 p.Gln250Glu 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/ift74-p-ile265val (accessed [today's date]).

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