Is PRMT1 p.Ile142Val (c.424A>G) pathogenic?

PRMT1 p.Ile142Val (c.424A>G) is classified Uncertain significance in PRMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.1052); Very rare (popmax 0.00134%, afr).

How common is PRMT1 p.Ile142Val (c.424A>G) in the general population?

PRMT1 p.Ile142Val (c.424A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PRMT1 p.Ile142Val (c.424A>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

PRMT1 p.Ile142Val

c.424A>G · VCV3310233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
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	18.08	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 0.00134% African / African-American · 1/74,750 alleles

Overall 6.2e-05% 1/1,613,194 alleles · very rare exomes 0/1,461,460 · genomes 1/151,734 · 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.Ile142Val
Coding: c.424A>G
MANE Select: NM_001536
Type: single nucleotide variant
Location: chr19:49683938 (GRCh38)
Gene constraint: LOEUF 0.218 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 8 PDB
Residue 142: 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-ile142val (accessed [today's date]).

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