Is AGO1 p.Ile150Phe (c.448A>T) pathogenic?

AGO1 p.Ile150Phe (c.448A>T) is classified Uncertain significance in AGO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely benign (0.1382); Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGO1 p.Ile150Phe (c.448A>T)?

AGO1 p.Ile150Phe (c.448A>T) is associated with Inborn genetic diseases (ClinVar).

How common is AGO1 p.Ile150Phe (c.448A>T) in the general population?

AGO1 p.Ile150Phe (c.448A>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about AGO1 p.Ile150Phe (c.448A>T)?

AlphaMissense predicts likely benign (score 0.1382) — an in-silico prediction, not a clinical call.

AGO1 p.Ile150Phe

c.448A>T · VCV3276138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1382 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1382	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.72	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 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 1,726 bp · p 2.7e-13 · regional, not allelic
Overall
CADD	24.1	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 0.000593% European (non-Finnish) · 7/1,180,020 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,102 alleles · very rare exomes 7/1,461,874 · genomes 0/152,228 · 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: AGO1
Protein: p.Ile150Phe
Coding: c.448A>T
MANE Select: NM_012199
Type: single nucleotide variant
Location: chr1:35893214 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 91.45 · 8 PDB

Full AGO1 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

AGO1 p.Ala103Val Uncertain significance ★★ ⚠ same condition
AGO1 p.Ala479Val Uncertain significance ★★ ⚠ same condition
AGO1 p.Glu681Val Uncertain significance ★★ ⚠ same condition
AGO1 p.Thr249Met Uncertain significance ★★ ⚠ same condition
AGO1 c.2466-1G>A Likely pathogenic ★ same condition
AGO1 p.Ala452Thr Likely pathogenic ★ same condition
AGO1 p.Gly199Cys Likely pathogenic ★ same condition
AGO1 p.Arg177His 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/ago1-p-ile150phe (accessed [today's date]).

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