Is EML1 p.His552Arg (c.1655A>G) pathogenic?

EML1 p.His552Arg (c.1655A>G) is classified Uncertain significance in EML1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.697); Very rare (popmax 0.00111%, sas); Associated with Inborn genetic diseases.

What condition is associated with EML1 p.His552Arg (c.1655A>G)?

EML1 p.His552Arg (c.1655A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EML1 p.His552Arg (c.1655A>G) in the general population?

EML1 p.His552Arg (c.1655A>G) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about EML1 p.His552Arg (c.1655A>G)?

AlphaMissense predicts likely pathogenic (score 0.697) — an in-silico prediction, not a clinical call.

EML1 p.His552Arg

c.1655A>G · VCV4248721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.697	likely pathogenic
REVEL	0.727	pathogenic-leaning
SaProt	LLR -12.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 41 kb · p 9.5e-19 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00111% South Asian · 1/90,018 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,457,730 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,018
European (non-Finnish)	0.00017%	589,591

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: EML1
Protein: p.His552Arg
Coding: c.1655A>G
MANE Select: NM_004434
Type: single nucleotide variant
Location: chr14:99914600 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 1 PDB
Residue 552: the 'tandem atypical propeller in emls' region; a UniProt-annotated variant site (in bh); a UniProt-annotated variant site (in)

Full EML1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EML1 p.Arg192His Uncertain significance ★★ ⚠ same condition
EML1 p.Arg450Gln Uncertain significance ★★ ⚠ same condition
EML1 p.Arg813His Uncertain significance ★★ ⚠ same condition
EML1 p.Cys369Phe Uncertain significance ★★ ⚠ same condition
EML1 p.Gln409Glu Uncertain significance ★★ ⚠ same condition
EML1 p.His351Gln Uncertain significance ★★ ⚠ same condition
EML1 p.Val253Met Uncertain significance ★★ ⚠ same condition
EML1 p.Val688Met Uncertain significance ★★ ⚠ same condition

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/eml1-p-his552arg (accessed [today's date]).

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