Is NSMCE3 p.Asp121= (c.363C>T) pathogenic?

NSMCE3 p.Asp121= (c.363C>T) is classified Likely benign in NSMCE3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). Very rare (popmax 0.00667%, afr).

How common is NSMCE3 p.Asp121= (c.363C>T) in the general population?

NSMCE3 p.Asp121= (c.363C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

NSMCE3 p.Asp121=

c.363C>T · rs778075945 · VCV2873775

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

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 1	GERP -3.8, phastCons 0.068
Overall
CADD	7.962	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,948 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00112% 18/1,614,094 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,990
East Asian	0.00223%	44,864
European (non-Finnish)	0.00102%	98,338

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: NSMCE3
Protein: p.Asp121=
Coding: c.363C>T
MANE Select: NM_138704
dbSNP: rs778075945
Type: single nucleotide variant
Location: chr15:29269343 (GRCh38)
Structure: AlphaFold pLDDT 76.08 · 5 PDB
Residue 121: the mage domain; an α-helix; the 'interaction with nsmce1' region

Full NSMCE3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NSMCE3 p.Ala32= Likely benign ★★ same type
NSMCE3 p.Asn272Asp Uncertain significance ★ ⚠ same type
NSMCE3 p.Asp164Asn Uncertain significance ★ ⚠ same type
NSMCE3 p.Leu202Met Uncertain significance ★ ⚠ same type
NSMCE3 p.Ser11Cys Uncertain significance ★ ⚠ same type
NSMCE3 p.Ala76= Likely benign ★ same type
NSMCE3 p.Arg133= Likely benign ★ same type
NSMCE3 p.Arg17= 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/nsmce3-p-asp121 (accessed [today's date]).

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