Is NSD1 p.Phe392= (c.1176C>T) pathogenic?

NSD1 p.Phe392= (c.1176C>T) is classified Likely benign in NSD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-02). Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with NSD1 p.Phe392= (c.1176C>T)?

NSD1 p.Phe392= (c.1176C>T) is associated with Inborn genetic diseases, Sotos syndrome (ClinVar).

How common is NSD1 p.Phe392= (c.1176C>T) in the general population?

NSD1 p.Phe392= (c.1176C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

NSD1 p.Phe392=

c.1176C>T · rs763543904 · VCV588374

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.2, phastCons 1
Overall
CADD	11.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,946 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.0026% 42/1,613,652 alleles · very rare exomes 39/1,461,820 · genomes 3/151,832 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,987
African / African-American	0.00401%	24,923
European (non-Finnish)	0.00271%	36,874
Remaining individualsnot grpmax-eligible	0.0016%	62,482
Finnishnot grpmax-eligible	0.00156%	63,930
South Asian	0.0011%	91,066

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.Phe392=
Coding: c.1176C>T
MANE Select: NM_022455
dbSNP: rs763543904
Type: single nucleotide variant
Location: chr5:177204232 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 45.26 · 4 PDB

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

Also linked: Sotos syndrome

Similar variants

NSD1 c.1064-2A>G Pathogenic/Likely pathogenic ★★ same condition
NSD1 c.3921+1G>A Likely pathogenic ★★ same condition
NSD1 c.4192+2T>G Pathogenic ★★ same condition
NSD1 c.4378+1G>A Pathogenic/Likely pathogenic ★★ same condition
NSD1 c.4766-2A>G Pathogenic/Likely pathogenic ★★ same condition
NSD1 c.4966+1G>A Pathogenic ★★ same condition
NSD1 c.4966+1G>C Likely pathogenic ★★ same condition
NSD1 c.5146+1G>A Pathogenic/Likely pathogenic ★★ 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-phe392 (accessed [today's date]).

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