Is IFT74 p.Thr565= (c.1695C>G) pathogenic?

IFT74 p.Thr565= (c.1695C>G) is classified Likely benign in IFT74 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-08-11). Very rare (popmax 0.00043%, nfe); Associated with IFT74-related disorder.

What condition is associated with IFT74 p.Thr565= (c.1695C>G)?

IFT74 p.Thr565= (c.1695C>G) is associated with IFT74-related disorder (ClinVar).

How common is IFT74 p.Thr565= (c.1695C>G) in the general population?

IFT74 p.Thr565= (c.1695C>G) is very rare (popmax 0.00043%, nfe) (gnomAD).

IFT74 p.Thr565=

c.1695C>G · VCV3357141

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00043%, nfe)

Conditions

IFT74-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP 0.99, phastCons 0.99
Overall
CADD	7.085	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00043% European (non-Finnish) · 5/1,161,550 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000315% 5/1,588,562 alleles · very rare exomes 4/1,436,940 · genomes 1/151,622 · joint denominator

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.Thr565=
Coding: c.1695C>G
MANE Select: NM_025103
Type: single nucleotide variant
Location: chr9:27062628 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 565: a UniProt-annotated variant site (in jbts40); the 'important for interaction with ift27' region

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

Disease context

IFT74-related disorder

Similar variants

IFT74 c.1685-1G>T Pathogenic/Likely pathogenic ★★ same condition
IFT74 p.Thr327Lys Uncertain significance ★★ ⚠ same condition
IFT74 p.Gln342Ter Conflicting classifications of pathogenicity ★ same condition
IFT74 p.Arg288Ter Likely pathogenic same condition
IFT74 c.1054+7363T>C Uncertain significance same condition
IFT74 c.1054+7400A>C Uncertain significance same condition
IFT74 c.1054+7405G>A Uncertain significance same condition
IFT74 p.Ala274Val 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-thr565 (accessed [today's date]).

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