Is PRMT3 p.His252Arg (c.755A>G) pathogenic?

PRMT3 p.His252Arg (c.755A>G) is classified Uncertain significance in PRMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.1371); Ultra-rare (popmax 0.038%, eas).

How common is PRMT3 p.His252Arg (c.755A>G) in the general population?

PRMT3 p.His252Arg (c.755A>G) is ultra-rare (popmax 0.038%, eas) (gnomAD).

What do computational predictors say about PRMT3 p.His252Arg (c.755A>G)?

AlphaMissense predicts likely benign (score 0.1371) — an in-silico prediction, not a clinical call.

PRMT3 p.His252Arg

c.755A>G · rs772006874 · VCV2534978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1371 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.038%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1371	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -13.02	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.43 · regional, not allelic
Overall
CADD	23.8	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 0.038% East Asian · 17/44,760 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00156% 25/1,601,482 alleles · ultra-rare exomes 23/1,449,262 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.038%	2,633
Remaining individualsnot grpmax-eligible	0.00322%	31,035
African / African-American	0.00134%	74,610
European (non-Finnish)	0.000428%	233,752

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: PRMT3
Protein: p.His252Arg
Coding: c.755A>G
MANE Select: NM_005788
dbSNP: rs772006874
Type: single nucleotide variant
Location: chr11:20402968 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.63 · 10 PDB
Residue 252: the sam-dependent mtase prmt-type domain; an α-helix; the 'mediates interaction with aldh1a1' region

Full PRMT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT3 p.Ala210Val Benign ★★ same type
PRMT3 p.Ala175Thr Uncertain significance ★ ⚠ same type
PRMT3 p.Ala210Glu Uncertain significance ★ ⚠ same type
PRMT3 p.Ala276Pro Uncertain significance ★ ⚠ same type
PRMT3 p.Ala31Thr Uncertain significance ★ ⚠ same type
PRMT3 p.Arg12Gln Uncertain significance ★ ⚠ same type
PRMT3 p.Arg180Cys Uncertain significance ★ ⚠ same type
PRMT3 p.Arg180His 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/prmt3-p-his252arg (accessed [today's date]).

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