Is IFT74 p.Arg385Ter (c.1153C>T) pathogenic?

IFT74 p.Arg385Ter (c.1153C>T) is classified Pathogenic in IFT74 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). Very rare (popmax 0.00446%, eas).

How common is IFT74 p.Arg385Ter (c.1153C>T) in the general population?

IFT74 p.Arg385Ter (c.1153C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

IFT74 p.Arg385Ter

c.1153C>T · rs200176242 · VCV2178456

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -3, phastCons 0.008
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,834 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.0031% 50/1,613,240 alleles · very rare exomes 45/1,460,928 · genomes 5/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,417
European (non-Finnish)	0.00373%	26,805
South Asian	0.0022%	45,504
Remaining individualsnot grpmax-eligible	0.0016%	62,442
African / African-American	0.00133%	75,004

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.Arg385Ter
Coding: c.1153C>T
MANE Select: NM_025103
dbSNP: rs200176242
Type: single nucleotide variant
Location: chr9:27047318 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 385: a UniProt-annotated variant site (in jbts40)

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

Similar variants

IFT74 p.Arg385Pro Uncertain significance ★ ⚠ same residue
IFT74 p.Arg385= Likely benign ★ same residue
IFT74 p.Arg385Gly Uncertain significance ⚠ same residue
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

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-arg385ter (accessed [today's date]).

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