Is PRMT5 p.Met529Val (c.1585A>G) pathogenic?

PRMT5 p.Met529Val (c.1585A>G) is classified Likely benign in PRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). AlphaMissense: likely benign (0.0442); Rare (popmax 0.135%, nfe).

How common is PRMT5 p.Met529Val (c.1585A>G) in the general population?

PRMT5 p.Met529Val (c.1585A>G) is rare (popmax 0.135%, nfe) (gnomAD).

What do computational predictors say about PRMT5 p.Met529Val (c.1585A>G)?

AlphaMissense predicts likely benign (score 0.0442) — an in-silico prediction, not a clinical call.

PRMT5 p.Met529Val

c.1585A>G · rs147575039 · VCV3025242

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0442 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0442	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -2.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.55	GERP -4.3, phastCons 0.001
Regional constraint	o/e 0.51	unconstrained · MANE · 4,028 bp · p 6.5e-25 · regional, not allelic
Overall
CADD	4.593	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 0.135% European (non-Finnish) · 1,593/1,178,062 alleles

Filtering AF 0.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.166% 2,671/1,611,896 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.8%	36
Remaining individualsnot grpmax-eligible	0.346%	289
European (non-Finnish)grpmax	0.135%	740
Admixed American	0.0317%	3,158
African / African-American	0.0173%	5,765
Finnishnot grpmax-eligible	0.00156%	64,010
South Asian	0.0011%	91,032

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met529Val
Coding: c.1585A>G
MANE Select: NM_006109
dbSNP: rs147575039
Type: single nucleotide variant
Location: chr14:22922554 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.68 · 94 PDB
Residue 529: the sam-dependent mtase prmt-type domain; the 'beta barrel' region; a β-strand

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

Similar variants

PRMT5 p.Met529Thr 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-met529val (accessed [today's date]).

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