Is PRMT1 p.Ile331Val (c.991A>G) pathogenic?

PRMT1 p.Ile331Val (c.991A>G) is classified Uncertain significance in PRMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-13). AlphaMissense: likely benign (0.1546); Very rare (popmax 0.00441%, nfe).

How common is PRMT1 p.Ile331Val (c.991A>G) in the general population?

PRMT1 p.Ile331Val (c.991A>G) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about PRMT1 p.Ile331Val (c.991A>G)?

AlphaMissense predicts likely benign (score 0.1546) — an in-silico prediction, not a clinical call.

PRMT1 p.Ile331Val

c.991A>G · rs368980947 · VCV2395389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1546	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -9.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 7,709 bp · p 9.6e-36 · regional, not allelic
Overall
CADD	21.4	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 0.00441% European (non-Finnish) · 52/1,179,040 alleles

Filtering AF 0.00343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00323% 52/1,611,110 alleles · very rare exomes 48/1,460,258 · genomes 4/150,852 · 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: PRMT1
Protein: p.Ile331Val
Coding: c.991A>G
MANE Select: NM_001536
dbSNP: rs368980947
Type: single nucleotide variant
Location: chr19:49686685 (GRCh38)
Gene constraint: LOEUF 0.218 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 8 PDB
Residue 331: the sam-dependent mtase prmt-type domain; a β-strand

Full PRMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT1 p.Glu45= Benign ★★ same type
PRMT1 p.Ala249Thr Uncertain significance ★ ⚠ same type
PRMT1 p.Ala44Pro Uncertain significance ★ ⚠ same type
PRMT1 p.Ala7Val Uncertain significance ★ ⚠ same type
PRMT1 p.Arg112His Uncertain significance ★ ⚠ same type
PRMT1 p.Arg195Gln Uncertain significance ★ same type
PRMT1 p.Arg206Gln Uncertain significance ★ ⚠ same type
PRMT1 p.Arg369Gln 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/prmt1-p-ile331val (accessed [today's date]).

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