Is PRMT9 p.Val640fs (c.1918dup) pathogenic?

PRMT9 p.Val640fs (c.1918dup) is classified Pathogenic in PRMT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). Very rare (popmax 0.00267%, afr); Associated with Neurodevelopmental abnormality.

What condition is associated with PRMT9 p.Val640fs (c.1918dup)?

PRMT9 p.Val640fs (c.1918dup) is associated with Neurodevelopmental abnormality (ClinVar).

How common is PRMT9 p.Val640fs (c.1918dup) in the general population?

PRMT9 p.Val640fs (c.1918dup) is very rare (popmax 0.00267%, afr) (gnomAD).

PRMT9 p.Val640fs

c.1918dup · rs1394475208 · VCV1704236

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Neurodevelopmental abnormality

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 1, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,928 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,002 alleles · very rare exomes 0/1,461,838 · genomes 2/152,164 · 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: PRMT9
Protein: p.Val640fs
Coding: c.1918dup
MANE Select: NM_138364
dbSNP: rs1394475208
Type: Duplication
Location: chr4:147653978 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 4 PDB
Residue 640: 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.Ile786fs Pathogenic ★ same condition
PRMT9 p.Gln382Lys Uncertain significance ★★ ⚠ same condition
PRMT9 c.576-2A>G Pathogenic ★ same condition
PRMT9 c.(846+1_847-1 Pathogenic ★ same condition
PRMT9 p.Arg359Ter Pathogenic ★ same condition
PRMT9 p.Gln382fs Pathogenic ★ same condition
PRMT9 p.Gln440Ter Pathogenic ★ same condition
PRMT9 p.Glu139Ter 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-val640fs (accessed [today's date]).

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