Is PRMT5 p.Arg385Trp (c.1153C>T) pathogenic?

PRMT5 p.Arg385Trp (c.1153C>T) is classified Uncertain significance in PRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.2007); Very rare (popmax 0.0022%, nfe).

How common is PRMT5 p.Arg385Trp (c.1153C>T) in the general population?

PRMT5 p.Arg385Trp (c.1153C>T) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about PRMT5 p.Arg385Trp (c.1153C>T)?

AlphaMissense predicts likely benign (score 0.2007) — an in-silico prediction, not a clinical call.

PRMT5 p.Arg385Trp

c.1153C>T · VCV3783449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2007 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2007	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -12.06	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 4,028 bp · p 6.5e-25 · regional, not allelic
Overall
CADD	29.4	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

Grpmax group 0.0022% European (non-Finnish) · 26/1,180,034 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.0018% 29/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,386
Remaining individualsnot grpmax-eligible	0.0016%	62,488
Finnishnot grpmax-eligible	0.00156%	64,008
South Asian	0.0011%	91,090

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: PRMT5
Protein: p.Arg385Trp
Coding: c.1153C>T
MANE Select: NM_006109
Type: single nucleotide variant
Location: chr14:22924316 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.68 · 94 PDB
Residue 385: the sam-dependent mtase prmt-type domain; a β-strand

Full PRMT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT5 p.Arg385Gln Uncertain significance ★ ⚠ same residue
PRMT5 p.His143= Benign ★★ same type
PRMT5 p.Leu81= Benign ★★ same type
PRMT5 p.Pro125= Benign ★★ same type
PRMT5 p.Ala552Ser Uncertain significance ★ ⚠ same type
PRMT5 p.Ala9Gly Uncertain significance ★ ⚠ same type
PRMT5 p.Arg377Gln Uncertain significance ★ ⚠ same type
PRMT5 p.Arg384Gln 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/prmt5-p-arg385trp (accessed [today's date]).

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