Is NSD3 p.Arg383Pro (c.1148G>C) pathogenic?

NSD3 p.Arg383Pro (c.1148G>C) is classified Benign in NSD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-08). AlphaMissense: ambiguous (0.4078); Low-frequency (popmax 1.06%, afr).

How common is NSD3 p.Arg383Pro (c.1148G>C) in the general population?

NSD3 p.Arg383Pro (c.1148G>C) is low-frequency (popmax 1.06%, afr) (gnomAD).

What do computational predictors say about NSD3 p.Arg383Pro (c.1148G>C)?

AlphaMissense predicts ambiguous (score 0.4078) — an in-silico prediction, not a clinical call.

NSD3 p.Arg383Pro

c.1148G>C · rs2234552 · VCV716914

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4078 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, afr)

Computational evidence

Protein change
AlphaMissense	0.4078	ambiguous
REVEL	0.513	indeterminate
SaProt	LLR -6.56	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,041 bp · p 0.0055 · regional, not allelic
Overall
CADD	23.9	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 1.06% African / African-American · 796/75,024 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.975%

Overall 0.054% 871/1,613,708 alleles · low-frequency exomes 414/1,461,460 · genomes 457/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.06%	94
Remaining individualsnot grpmax-eligible	0.072%	1,389
Middle Eastern	0.033%	3,030
Admixed American	0.0283%	3,530
South Asian	0.0022%	45,526
European (non-Finnish)	0.000763%	131,095

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: NSD3
Protein: p.Arg383Pro
Coding: c.1148G>C
MANE Select: NM_023034
dbSNP: rs2234552
Type: single nucleotide variant
Location: chr8:38329811 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.29 · 25 PDB
Residue 383: a UniProt-annotated variant site (in); an α-helix

Full NSD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NSD3 p.Arg383Gln Uncertain significance ★ ⚠ same residue
NSD3 p.Arg383Gly Uncertain significance ★ same residue
NSD3 p.Ala1212= Benign ★★ same type
NSD3 p.Asn987= Benign ★★ same type
NSD3 p.Ser754Leu Benign ★★ same type
NSD3 p.Ser855Gly Benign ★★ same type
NSD3 p.Thr186Met Benign ★★ same type
NSD3 p.Thr556Met Likely benign ★★ 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/nsd3-p-arg383pro (accessed [today's date]).

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