Is EMB p.Phe241Leu (c.723C>A) pathogenic?

EMB p.Phe241Leu (c.723C>A) is classified Uncertain significance in EMB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). AlphaMissense: likely pathogenic (0.9698); Ultra-rare (popmax 0.0103%, nfe).

How common is EMB p.Phe241Leu (c.723C>A) in the general population?

EMB p.Phe241Leu (c.723C>A) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about EMB p.Phe241Leu (c.723C>A)?

AlphaMissense predicts likely pathogenic (score 0.9698) — an in-silico prediction, not a clinical call.

EMB p.Phe241Leu

c.723C>A · rs377652531 · VCV2507724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9698 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9698	likely pathogenic
REVEL	0.551	indeterminate
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.86, phastCons 1
Overall
CADD	22.3	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 0.0103% European (non-Finnish) · 122/1,179,228 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00828%

Overall 0.008% 129/1,612,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,666
African / African-American	0.00535%	18,690
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,550
Admixed American	0.00167%	59,790
Remaining individualsnot grpmax-eligible	0.0016%	62,402

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.Phe241Leu
Coding: c.723C>A
MANE Select: NM_003400 · reported on NM_198449
dbSNP: rs377652531
Type: single nucleotide variant
Location: chr5:50403332 (GRCh38)
Structure: AlphaFold pLDDT 91.62 · 19 PDB
Residue 241: 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-phe241leu (accessed [today's date]).

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