Is IFT74 p.Ala68Ser (c.202G>T) pathogenic?

IFT74 p.Ala68Ser (c.202G>T) is classified Uncertain significance in IFT74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-18). AlphaMissense: likely benign (0.0882); Absent from gnomAD v4.1.

How common is IFT74 p.Ala68Ser (c.202G>T) in the general population?

IFT74 p.Ala68Ser (c.202G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT74 p.Ala68Ser (c.202G>T)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

IFT74 p.Ala68Ser

c.202G>T · rs757910179 · VCV2069790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.38	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 7.5	GERP 0.76, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	20.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IFT74
Protein: p.Ala68Ser
Coding: c.202G>T
MANE Select: NM_025103
dbSNP: rs757910179
Type: single nucleotide variant
Location: chr9:26978209 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 68: 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

Similar variants

IFT74 p.Ala68Gly Uncertain significance ★ ⚠ same residue
IFT74 p.Ala68= Likely benign ★ 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
IFT74 p.Ala558Val 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-ala68ser (accessed [today's date]).

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