Is PRMT3 p.Ser343Phe (c.1028C>T) pathogenic?

PRMT3 p.Ser343Phe (c.1028C>T) is classified Uncertain significance in PRMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely pathogenic (0.9845); Very rare (popmax 0.00134%, afr).

How common is PRMT3 p.Ser343Phe (c.1028C>T) in the general population?

PRMT3 p.Ser343Phe (c.1028C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PRMT3 p.Ser343Phe (c.1028C>T)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

PRMT3 p.Ser343Phe

c.1028C>T · rs774885478 · VCV2623545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic · top 6% in PRMT3
REVEL	0.621	indeterminate
SaProt	LLR -13.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.43 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00134% African / African-American · 1/74,862 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000559% 9/1,610,736 alleles · very rare exomes 9/1,458,640 · genomes 0/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,862
European (non-Finnish)	0.000679%	147,190

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.Ser343Phe
Coding: c.1028C>T
MANE Select: NM_005788
dbSNP: rs774885478
Type: single nucleotide variant
Location: chr11:20452164 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.63 · 10 PDB
Residue 343: a binding site; 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-ser343phe (accessed [today's date]).

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