Is EMB p.Val72Ala (c.215T>C) pathogenic?

EMB p.Val72Ala (c.215T>C) is classified Uncertain significance in EMB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0934); Very rare (popmax 0.0051%, amr).

How common is EMB p.Val72Ala (c.215T>C) in the general population?

EMB p.Val72Ala (c.215T>C) is very rare (popmax 0.0051%, amr) (gnomAD).

What do computational predictors say about EMB p.Val72Ala (c.215T>C)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

EMB p.Val72Ala

c.215T>C · VCV3508135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0051%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.92	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 2.8	GERP 1.7, phastCons 0.026
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

Grpmax group 0.0051% Admixed American · 3/58,848 alleles

Filtering AF 0.00135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000675%

Overall 0.000561% 9/1,603,344 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0051%	19,616
Remaining individualsnot grpmax-eligible	0.00161%	62,028
European (non-Finnish)	0.000426%	234,845

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.Val72Ala
Coding: c.215T>C
MANE Select: NM_003400 · reported on NM_198449
Type: single nucleotide variant
Location: chr5:50411365 (GRCh38)
Structure: AlphaFold pLDDT 91.62 · 19 PDB
Residue 72: the importin n-terminal domain; the 'necessary for htlv-1 rex-mediated mrna export' region

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-val72ala (accessed [today's date]).

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