Is IFT74 p.Pro42Thr (c.124C>A) pathogenic?

IFT74 p.Pro42Thr (c.124C>A) is classified Uncertain significance in IFT74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.00317%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IFT74 p.Pro42Thr (c.124C>A)?

IFT74 p.Pro42Thr (c.124C>A) is associated with Inborn genetic diseases (ClinVar).

How common is IFT74 p.Pro42Thr (c.124C>A) in the general population?

IFT74 p.Pro42Thr (c.124C>A) is very rare (popmax 0.00317%, nfe) (gnomAD).

What do computational predictors say about IFT74 p.Pro42Thr (c.124C>A)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

IFT74 p.Pro42Thr

c.124C>A · rs1230545252 · VCV2225409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00317%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.08	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 3.2	GERP 0.64, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	17.44	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 0.00317% European (non-Finnish) · 37/1,167,832 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00204%

Overall 0.00235% 37/1,573,846 alleles · very rare exomes 36/1,421,774 · genomes 1/152,072 · 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.Pro42Thr
Coding: c.124C>A
MANE Select: NM_025103
dbSNP: rs1230545252
Type: single nucleotide variant
Location: chr9:26978131 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 42: 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.Pro42= Likely benign ★ 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-pro42thr (accessed [today's date]).

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