Is PRMT7 p.Pro459= (c.1377G>A) pathogenic?

PRMT7 p.Pro459= (c.1377G>A) is classified Likely benign in PRMT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). Very rare (popmax 0.00933%, nfe).

How common is PRMT7 p.Pro459= (c.1377G>A) in the general population?

PRMT7 p.Pro459= (c.1377G>A) is very rare (popmax 0.00933%, nfe) (gnomAD).

PRMT7 p.Pro459=

c.1377G>A · rs202214387 · VCV2907672

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00933%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -5.5, phastCons 0.094
Overall
CADD	4.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00933% European (non-Finnish) · 110/1,178,878 alleles

Filtering AF 0.00791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00893% 144/1,612,748 alleles · very rare exomes 132/1,460,540 · genomes 12/152,208 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0453%	2,207
European (non-Finnish)grpmax	0.00933%	10,717
Remaining individualsnot grpmax-eligible	0.0048%	20,819
Admixed American	0.00333%	29,988

Finnish 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: PRMT7
Protein: p.Pro459=
Coding: c.1377G>A
MANE Select: NM_019023
dbSNP: rs202214387
Type: single nucleotide variant
Location: chr16:68348395 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 459: the sam-dependent mtase prmt-type 2 domain

Full PRMT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT7 c.1056-1G>T Pathogenic/Likely pathogenic ★★ same type
PRMT7 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same type
PRMT7 p.Arg390Ter Pathogenic ★★ same type
PRMT7 p.Cys571Ter Pathogenic ★★ same type
PRMT7 p.Gln323Ter Pathogenic ★★ same type
PRMT7 p.Glu108Ter Pathogenic/Likely pathogenic ★★ same type
PRMT7 p.Tyr159Ter Pathogenic ★★ same type
PRMT7 p.Ala162Thr 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/prmt7-p-pro459 (accessed [today's date]).

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