Is PRMT9 p.Phe591Ser (c.1772T>C) pathogenic?

PRMT9 p.Phe591Ser (c.1772T>C) is classified Uncertain significance in PRMT9 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-02). AlphaMissense: likely pathogenic (0.9632); Absent from gnomAD v4.1; Associated with Neurodevelopmental abnormality.

What condition is associated with PRMT9 p.Phe591Ser (c.1772T>C)?

PRMT9 p.Phe591Ser (c.1772T>C) is associated with Neurodevelopmental abnormality (ClinVar).

How common is PRMT9 p.Phe591Ser (c.1772T>C) in the general population?

PRMT9 p.Phe591Ser (c.1772T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRMT9 p.Phe591Ser (c.1772T>C)?

AlphaMissense predicts likely pathogenic (score 0.9632) — an in-silico prediction, not a clinical call.

PRMT9 p.Phe591Ser

c.1772T>C · rs2530618696 · VCV1704235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9632 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Neurodevelopmental abnormality

Computational evidence

Protein change
AlphaMissense	0.9632	likely pathogenic · top 6% in PRMT9
REVEL	0.252	benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 45 kb · p 0.019 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRMT9
Protein: p.Phe591Ser
Coding: c.1772T>C
MANE Select: NM_138364
dbSNP: rs2530618696
Type: single nucleotide variant
Location: chr4:147654125 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 4 PDB
Residue 591: the sam-dependent mtase prmt-type 2 domain

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

Disease context

Neurodevelopmental abnormality — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRMT9 p.Gln382Lys Uncertain significance ★★ ⚠ same condition
PRMT9 c.576-2A>G Pathogenic ★ same condition
PRMT9 p.Arg359Ter Pathogenic ★ same condition
PRMT9 p.Gln440Ter Pathogenic ★ same condition
PRMT9 p.Glu139Ter Pathogenic ★ same condition
PRMT9 p.Gly189Arg Pathogenic ★ same condition
PRMT9 p.Leu86Ter Pathogenic ★ same condition
PRMT9 p.Trp73Ter Pathogenic ★ same condition

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-phe591ser (accessed [today's date]).

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