Is PRMT9 p.Ala16Pro (c.46G>C) pathogenic?

PRMT9 p.Ala16Pro (c.46G>C) is classified Uncertain significance in PRMT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: likely benign (0.0977); Ultra-rare (popmax 0.0357%, eas).

How common is PRMT9 p.Ala16Pro (c.46G>C) in the general population?

PRMT9 p.Ala16Pro (c.46G>C) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about PRMT9 p.Ala16Pro (c.46G>C)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

PRMT9 p.Ala16Pro

c.46G>C · rs201765298 · VCV3218962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -8.69	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 -0.36	GERP -2.5, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 45 kb · p 0.019 · regional, not allelic
Overall
CADD	13.57	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 0.0357% East Asian · 16/44,868 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00105% 17/1,612,914 alleles · ultra-rare exomes 12/1,460,628 · genomes 5/152,286 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,804
European (non-Finnish)	8.48e-05%	1,179,702

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: PRMT9
Protein: p.Ala16Pro
Coding: c.46G>C
MANE Select: NM_138364
dbSNP: rs201765298
Type: single nucleotide variant
Location: chr4:147683942 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 4 PDB

Full PRMT9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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PRMT9 p.Arg359Ter Pathogenic ★ same type
PRMT9 p.Gln440Ter Pathogenic ★ same type
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PRMT9 p.Gly189Arg Pathogenic ★ same type
PRMT9 p.Leu86Ter Pathogenic ★ 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/prmt9-p-ala16pro (accessed [today's date]).

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