Is NSUN2 p.Val204= (c.612C>A) pathogenic?

NSUN2 p.Val204= (c.612C>A) is classified Benign/Likely benign in NSUN2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3%, afr); Associated with Inborn genetic diseases.

What condition is associated with NSUN2 p.Val204= (c.612C>A)?

NSUN2 p.Val204= (c.612C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NSUN2 p.Val204= (c.612C>A) in the general population?

NSUN2 p.Val204= (c.612C>A) is low-frequency (popmax 3%, afr) (gnomAD).

NSUN2 p.Val204=

c.612C>A · rs148924682 · VCV588379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3%, 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 0.2	GERP -4.3, phastCons 0.85
Overall
CADD	5.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3% African / African-American · 2,252/75,028 alleles

Filtering AF 2.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.86%

Overall 0.164% 2,641/1,613,692 alleles · low-frequency exomes 1,225/1,461,350 · genomes 1,416/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3%	33
Admixed American	0.258%	387
Remaining individualsnot grpmax-eligible	0.237%	422
Middle Eastern	0.198%	505
South Asian	0.00659%	15,181
European (non-Finnish)	0.00576%	17,347

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.Val204=
Coding: c.612C>A
MANE Select: NM_017755
dbSNP: rs148924682
Type: single nucleotide variant
Location: chr5:6622026 (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.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
NSUN2 p.Arg8Gln Uncertain significance ★★ ⚠ same condition
NSUN2 p.Asn547Asp 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-val204 (accessed [today's date]).

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