Is NSD1 p.Pro360Ser (c.1078C>T) pathogenic?

NSD1 p.Pro360Ser (c.1078C>T) is classified Uncertain significance in NSD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: likely pathogenic (0.6429); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with NSD1 p.Pro360Ser (c.1078C>T)?

NSD1 p.Pro360Ser (c.1078C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NSD1 p.Pro360Ser (c.1078C>T) in the general population?

NSD1 p.Pro360Ser (c.1078C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about NSD1 p.Pro360Ser (c.1078C>T)?

AlphaMissense predicts likely pathogenic (score 0.6429) — an in-silico prediction, not a clinical call.

NSD1 p.Pro360Ser

c.1078C>T · rs2149836107 · VCV2552378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6429	likely pathogenic
REVEL	0.363	indeterminate
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 18 kb · p 1e-09 · regional, not allelic
Overall
CADD	28.0	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 0.00223% East Asian · 1/44,872 alleles

Overall 6.2e-05% 1/1,613,956 alleles · very rare exomes 1/1,461,722 · genomes 0/152,234 · joint denominator

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: NSD1
Protein: p.Pro360Ser
Coding: c.1078C>T
MANE Select: NM_022455
dbSNP: rs2149836107
Type: single nucleotide variant
Location: chr5:177204134 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 45.26 · 4 PDB
Residue 360: the pwwp 1 domain

Full NSD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NSD1 p.Pro360Ala Uncertain significance ★ same residue
NSD1 c.5622+1G>A Pathogenic/Likely pathogenic ★★ same condition
NSD1 p.Trp1709Ter Pathogenic ★★ same condition
NSD1 p.Ala1850Val Uncertain significance ★★ ⚠ same condition
NSD1 p.Ala2300Val Uncertain significance ★★ ⚠ same condition
NSD1 p.Ala2630Asp Uncertain significance ★★ ⚠ same condition
NSD1 p.Arg106Lys Uncertain significance ★★ ⚠ same condition
NSD1 p.Arg1587His Uncertain significance ★★ ⚠ same condition

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/nsd1-p-pro360ser (accessed [today's date]).

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