Is PRMT5 p.Asp347Glu (c.1041C>G) pathogenic?

PRMT5 p.Asp347Glu (c.1041C>G) is classified Uncertain significance in PRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: likely benign (0.285); Very rare (popmax 6.84e-05%).

How common is PRMT5 p.Asp347Glu (c.1041C>G) in the general population?

PRMT5 p.Asp347Glu (c.1041C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about PRMT5 p.Asp347Glu (c.1041C>G)?

AlphaMissense predicts likely benign (score 0.285) — an in-silico prediction, not a clinical call.

PRMT5 p.Asp347Glu

c.1041C>G · VCV3310248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.285	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.49, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 4,028 bp · p 6.5e-25 · regional, not allelic
Overall
CADD	22.0	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 6.84e-05%

Overall 6.84e-05% 1/1,461,830 alleles · very rare

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: PRMT5
Protein: p.Asp347Glu
Coding: c.1041C>G
MANE Select: NM_006109
Type: single nucleotide variant
Location: chr14:22924514 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.68 · 94 PDB
Residue 347: 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-asp347glu (accessed [today's date]).

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