Is PRMT3 p.Ser492Ala (c.1474T>G) pathogenic?

PRMT3 p.Ser492Ala (c.1474T>G) is classified Uncertain significance in PRMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.0633); Ultra-rare (popmax 0.02%, amr).

How common is PRMT3 p.Ser492Ala (c.1474T>G) in the general population?

PRMT3 p.Ser492Ala (c.1474T>G) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about PRMT3 p.Ser492Ala (c.1474T>G)?

AlphaMissense predicts likely benign (score 0.0633) — an in-silico prediction, not a clinical call.

PRMT3 p.Ser492Ala

c.1474T>G · rs759796017 · VCV2473861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0633 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0633	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -7.25	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 1.2	GERP -1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.43 · regional, not allelic
Overall
CADD	15.22	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,852 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.009%

Overall 0.00244% 39/1,595,472 alleles · ultra-rare exomes 32/1,443,228 · genomes 7/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,988
European (non-Finnish)	0.00232%	43,086

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.Ser492Ala
Coding: c.1474T>G
MANE Select: NM_005788
dbSNP: rs759796017
Type: single nucleotide variant
Location: chr11:20494242 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.63 · 10 PDB
Residue 492: the sam-dependent mtase prmt-type domain; the 'mediates interaction with aldh1a1' region; a β-strand

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-ser492ala (accessed [today's date]).

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