Is EMB p.Asn75Asp (c.223A>G) pathogenic?

EMB p.Asn75Asp (c.223A>G) is classified Uncertain significance in EMB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1853); Absent from gnomAD v4.1.

How common is EMB p.Asn75Asp (c.223A>G) in the general population?

EMB p.Asn75Asp (c.223A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMB p.Asn75Asp (c.223A>G)?

AlphaMissense predicts likely benign (score 0.1853) — an in-silico prediction, not a clinical call.

EMB p.Asn75Asp

c.223A>G · VCV4248570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1853 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1853	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.47, phastCons 1
Overall
CADD	21.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EMB
Protein: p.Asn75Asp
Coding: c.223A>G
MANE Select: NM_003400 · reported on NM_198449
Type: single nucleotide variant
Location: chr5:50411357 (GRCh38)
Structure: AlphaFold pLDDT 91.62 · 19 PDB
Residue 75: 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

EMB p.Asn75Lys Uncertain significance ★ ⚠ same residue
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

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-asn75asp (accessed [today's date]).

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