Is NSUN2 p.Pro39= (c.117C>T) pathogenic?

NSUN2 p.Pro39= (c.117C>T) is classified Likely benign in NSUN2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-13). Rare (popmax 0.16%, afr); Associated with Inborn genetic diseases.

What condition is associated with NSUN2 p.Pro39= (c.117C>T)?

NSUN2 p.Pro39= (c.117C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NSUN2 p.Pro39= (c.117C>T) in the general population?

NSUN2 p.Pro39= (c.117C>T) is rare (popmax 0.16%, afr) (gnomAD).

NSUN2 p.Pro39=

c.117C>T · rs138016489 · VCV588110

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.16%, afr)

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 0.21	GERP -2.6, phastCons 0.92
Overall
CADD	11.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% African / African-American · 120/75,032 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.00799% 129/1,613,976 alleles · rare exomes 51/1,461,694 · genomes 78/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.16%	625
Remaining individualsnot grpmax-eligible	0.008%	12,499
Admixed American	0.00333%	30,009
European (non-Finnish)	0.00017%	589,967

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: NSUN2
Protein: p.Pro39=
Coding: c.117C>T
MANE Select: NM_017755
dbSNP: rs138016489
Type: single nucleotide variant
Location: chr5:6632736 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.09 · 11 PDB

Full NSUN2 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

NSUN2 p.Pro39Leu Uncertain significance ★★ ⚠ same residue
NSUN2 p.Pro39His Uncertain significance ★ ⚠ same residue
NSUN2 p.Ala485Val Uncertain significance ★★ ⚠ same condition
NSUN2 p.Ala649Thr Uncertain significance ★★ ⚠ same condition
NSUN2 p.Arg175Trp Uncertain significance ★★ ⚠ same condition
NSUN2 p.Arg389Gln Uncertain significance ★★ ⚠ same condition
NSUN2 p.Arg438His Uncertain significance ★★ ⚠ same condition
NSUN2 p.Arg737Thr 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/nsun2-p-pro39 (accessed [today's date]).

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