Is PRMT1 p.Ala44Pro (c.130G>C) pathogenic?

PRMT1 p.Ala44Pro (c.130G>C) is classified Uncertain significance in PRMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely benign (0.1329); Ultra-rare (popmax 0.0617%, amr).

How common is PRMT1 p.Ala44Pro (c.130G>C) in the general population?

PRMT1 p.Ala44Pro (c.130G>C) is ultra-rare (popmax 0.0617%, amr) (gnomAD).

What do computational predictors say about PRMT1 p.Ala44Pro (c.130G>C)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

PRMT1 p.Ala44Pro

c.130G>C · rs763394313 · VCV2405841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -6.01	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 12	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 3,251 bp · p 0.73 · 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 0.0617% Admixed American · 37/60,008 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0405%

Overall 0.00273% 44/1,614,020 alleles · ultra-rare exomes 43/1,461,828 · genomes 1/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0617%	1,622
Middle Eastern	0.0164%	6,084
East Asian	0.00223%	44,894
South Asian	0.0011%	91,086
European (non-Finnish)	0.000339%	295,002

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.Ala44Pro
Coding: c.130G>C
MANE Select: NM_001536
dbSNP: rs763394313
Type: single nucleotide variant
Location: chr19:49680526 (GRCh38)
Gene constraint: LOEUF 0.218 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 8 PDB
Residue 44: an α-helix

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.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
PRMT1 p.Asn20Lys 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-ala44pro (accessed [today's date]).

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