Is EMB p.Asn189His (c.565A>C) pathogenic?

EMB p.Asn189His (c.565A>C) is classified Uncertain significance in EMB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1059); Ultra-rare (popmax 0.0534%, sas).

How common is EMB p.Asn189His (c.565A>C) in the general population?

EMB p.Asn189His (c.565A>C) is ultra-rare (popmax 0.0534%, sas) (gnomAD).

What do computational predictors say about EMB p.Asn189His (c.565A>C)?

AlphaMissense predicts likely benign (score 0.1059) — an in-silico prediction, not a clinical call.

EMB p.Asn189His

c.565A>C · VCV4248564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1059 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1059	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.9	GERP -0.84, phastCons 0.99
Overall
CADD	13.36	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

Grpmax group 0.0534% South Asian · 48/89,920 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0371%

Overall 0.00305% 49/1,606,644 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0534%	1,873
East Asian	0.00224%	44,578

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.Asn189His
Coding: c.565A>C
MANE Select: NM_003400 · reported on NM_198449
Type: single nucleotide variant
Location: chr5:50405760 (GRCh38)
Structure: AlphaFold pLDDT 91.62 · 19 PDB
Residue 189: 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-asn189his (accessed [today's date]).

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