Is EMB p.Lys321Asn (c.963A>T) pathogenic?

EMB p.Lys321Asn (c.963A>T) is classified Uncertain significance in EMB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: ambiguous (0.4167); Absent from gnomAD v4.1.

How common is EMB p.Lys321Asn (c.963A>T) in the general population?

EMB p.Lys321Asn (c.963A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMB p.Lys321Asn (c.963A>T)?

AlphaMissense predicts ambiguous (score 0.4167) — an in-silico prediction, not a clinical call.

EMB p.Lys321Asn

c.963A>T · rs2478084261 · VCV2330270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4167 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,604,396)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4167	ambiguous
REVEL	0.095	moderately benign-leaning
SaProt	LLR -8.17	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.44, phastCons 1
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,604,396). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMB
Protein: p.Lys321Asn
Coding: c.963A>T
MANE Select: NM_003400 · reported on NM_198449
dbSNP: rs2478084261
Type: single nucleotide variant
Location: chr5:50399862 (GRCh38)
Structure: AlphaFold pLDDT 91.62 · 19 PDB
Residue 321: 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-lys321asn (accessed [today's date]).

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