Is PRMT3 p.Pro512Ser (c.1534C>T) pathogenic?

PRMT3 p.Pro512Ser (c.1534C>T) is classified Uncertain significance in PRMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.2728); Very rare (popmax 0.0011%, sas).

How common is PRMT3 p.Pro512Ser (c.1534C>T) in the general population?

PRMT3 p.Pro512Ser (c.1534C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PRMT3 p.Pro512Ser (c.1534C>T)?

AlphaMissense predicts likely benign (score 0.2728) — an in-silico prediction, not a clinical call.

PRMT3 p.Pro512Ser

c.1534C>T · VCV3310243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2728	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.43 · regional, not allelic
Overall
CADD	22.7	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 0.0011% South Asian · 1/91,028 alleles

Overall 0.000186% 3/1,612,426 alleles · very rare exomes 3/1,460,230 · genomes 0/152,196 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
South Asiangrpmax	0.0011%	91,028
European (non-Finnish)	8.48e-05%	1,178,602

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: PRMT3
Protein: p.Pro512Ser
Coding: c.1534C>T
MANE Select: NM_005788
Type: single nucleotide variant
Location: chr11:20508351 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.63 · 10 PDB
Residue 512: the sam-dependent mtase prmt-type domain; 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-pro512ser (accessed [today's date]).

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