Is EMB p.Asn83Asp (c.247A>G) pathogenic?

EMB p.Asn83Asp (c.247A>G) is classified Uncertain significance in EMB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0922); Ultra-rare (popmax 0.0121%, sas).

How common is EMB p.Asn83Asp (c.247A>G) in the general population?

EMB p.Asn83Asp (c.247A>G) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about EMB p.Asn83Asp (c.247A>G)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

EMB p.Asn83Asp

c.247A>G · rs756134551 · VCV2518367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -5.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -3.4
Overall
CADD	0.123	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/90,840 alleles

Filtering AF 0.00678% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00523%

Overall 0.000744% 12/1,612,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,258
Admixed American	0.00167%	59,850

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: EMB
Protein: p.Asn83Asp
Coding: c.247A>G
MANE Select: NM_003400 · reported on NM_198449
dbSNP: rs756134551
Type: single nucleotide variant
Location: chr5:50411333 (GRCh38)
Structure: AlphaFold pLDDT 91.62 · 19 PDB
Residue 83: the importin n-terminal domain; the 'necessary for htlv-1 rex-mediated mrna export' region; an α-helix

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

Similar variants

XPO1 c.888+9A>G Benign ★★ same type
XPO1 p.Arg305= Benign ★★ same type
XPO1 p.Leu625= Likely benign ★★ same type
XPO1 p.Lys757= Likely benign ★★ same type
XPO1 p.Thr846= Benign ★★ same type
XPO1 c.1887+1G>T Pathogenic ★ same type
XPO1 c.888+1G>A Pathogenic ★ same type
XPO1 p.Arg765Ter Pathogenic ★ 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/emb-p-asn83asp (accessed [today's date]).

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