Is AGO1 p.Pro371Ser (c.1111C>T) pathogenic?

AGO1 p.Pro371Ser (c.1111C>T) is classified Uncertain significance in AGO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.8393); Absent from gnomAD v4.1.

How common is AGO1 p.Pro371Ser (c.1111C>T) in the general population?

AGO1 p.Pro371Ser (c.1111C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGO1 p.Pro371Ser (c.1111C>T)?

AlphaMissense predicts likely pathogenic (score 0.8393) — an in-silico prediction, not a clinical call.

AGO1 p.Pro371Ser

c.1111C>T · rs2148715372 · VCV1305114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8393 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8393	likely pathogenic
REVEL	0.308	indeterminate
SaProt	LLR -13.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 7,259 bp · p 4e-17 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: AGO1
Protein: p.Pro371Ser
Coding: c.1111C>T
MANE Select: NM_012199
dbSNP: rs2148715372
Type: single nucleotide variant
Location: chr1:35901564 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 91.45 · 8 PDB
Residue 371: an α-helix

Full AGO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGO1 p.Asp356Asn Likely pathogenic ★★ same type
AGO1 p.Gly199Ser Pathogenic/Likely pathogenic ★★ same type
AGO1 p.Pro189Leu Likely pathogenic ★★ same type
AGO1 p.Ala103Val Uncertain significance ★★ ⚠ same type
AGO1 p.Ala413Val Uncertain significance ★★ ⚠ same type
AGO1 p.Ala479Val Uncertain significance ★★ ⚠ same type
AGO1 p.Arg26Gln Uncertain significance ★★ ⚠ same type
AGO1 p.Arg284His 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/ago1-p-pro371ser (accessed [today's date]).

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