Is PRMT5 p.Ile341Val (c.1021A>G) pathogenic?

PRMT5 p.Ile341Val (c.1021A>G) is classified Uncertain significance in PRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0583); Absent from gnomAD v4.1.

How common is PRMT5 p.Ile341Val (c.1021A>G) in the general population?

PRMT5 p.Ile341Val (c.1021A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRMT5 p.Ile341Val (c.1021A>G)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

PRMT5 p.Ile341Val

c.1021A>G · VCV3425530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -5.62	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 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 4,028 bp · p 6.5e-25 · regional, not allelic
Overall
CADD	19.46	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: PRMT5
Protein: p.Ile341Val
Coding: c.1021A>G
MANE Select: NM_006109
Type: single nucleotide variant
Location: chr14:22924534 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.68 · 94 PDB
Residue 341: the sam-dependent mtase prmt-type domain; an α-helix

Full PRMT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT5 p.His143= Benign ★★ same type
PRMT5 p.Leu81= Benign ★★ same type
PRMT5 p.Pro125= Benign ★★ same type
PRMT5 p.Ala552Ser Uncertain significance ★ ⚠ same type
PRMT5 p.Ala9Gly Uncertain significance ★ ⚠ same type
PRMT5 p.Arg377Gln Uncertain significance ★ ⚠ same type
PRMT5 p.Arg384Gln Uncertain significance ★ ⚠ same type
PRMT5 p.Arg385Gln 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/prmt5-p-ile341val (accessed [today's date]).

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