Is EML1 p.Cys369Phe (c.1106G>T) pathogenic?

EML1 p.Cys369Phe (c.1106G>T) is classified Uncertain significance in EML1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.8382); Ultra-rare (popmax 0.0136%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EML1 p.Cys369Phe (c.1106G>T)?

EML1 p.Cys369Phe (c.1106G>T) is associated with Inborn genetic diseases (ClinVar).

How common is EML1 p.Cys369Phe (c.1106G>T) in the general population?

EML1 p.Cys369Phe (c.1106G>T) is ultra-rare (popmax 0.0136%, nfe) (gnomAD).

What do computational predictors say about EML1 p.Cys369Phe (c.1106G>T)?

AlphaMissense predicts likely pathogenic (score 0.8382) — an in-silico prediction, not a clinical call.

EML1 p.Cys369Phe

c.1106G>T · rs372044881 · VCV1417354

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8382 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8382	likely pathogenic
REVEL	0.555	indeterminate
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.8	GERP 0.82, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 41 kb · p 9.5e-19 · regional, not allelic
Overall
CADD	33.0	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 0.0136% European (non-Finnish) · 161/1,180,026 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.01% 162/1,613,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0136%	7,329
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Cys369Phe
Coding: c.1106G>T
MANE Select: NM_004434
dbSNP: rs372044881
Type: single nucleotide variant
Location: chr14:99909346 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 1 PDB
Residue 369: the 'tandem atypical propeller in emls' region

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

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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
EML1 c.384-3507C>T 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-cys369phe (accessed [today's date]).

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