Is IFT74 p.Ser50Phe (c.149C>T) pathogenic?

IFT74 p.Ser50Phe (c.149C>T) is classified Uncertain significance in IFT74 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely benign (0.2236); Ultra-rare (popmax 0.0202%, eas); Associated with Inborn genetic diseases.

What condition is associated with IFT74 p.Ser50Phe (c.149C>T)?

IFT74 p.Ser50Phe (c.149C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IFT74 p.Ser50Phe (c.149C>T) in the general population?

IFT74 p.Ser50Phe (c.149C>T) is ultra-rare (popmax 0.0202%, eas) (gnomAD).

What do computational predictors say about IFT74 p.Ser50Phe (c.149C>T)?

AlphaMissense predicts likely benign (score 0.2236) — an in-silico prediction, not a clinical call.

IFT74 p.Ser50Phe

c.149C>T · rs546127878 · VCV1926878

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2236 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2236	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -11.81	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0202% East Asian · 9/44,502 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.000622% 10/1,608,082 alleles · ultra-rare exomes 6/1,455,834 · genomes 4/152,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0202%	4,945
Remaining individualsnot grpmax-eligible	0.00161%	62,268

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.Ser50Phe
Coding: c.149C>T
MANE Select: NM_025103
dbSNP: rs546127878
Type: single nucleotide variant
Location: chr9:26978156 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 50: the 'basic region' region; 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.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
IFT74 p.Gln335Lys 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-ser50phe (accessed [today's date]).

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