Is EED p.Arg52Cys (c.154C>T) pathogenic?

EED p.Arg52Cys (c.154C>T) is classified Uncertain significance in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-01). AlphaMissense: likely pathogenic (0.7548); Very rare (popmax 0.00174%, amr); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with EED p.Arg52Cys (c.154C>T)?

EED p.Arg52Cys (c.154C>T) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is EED p.Arg52Cys (c.154C>T) in the general population?

EED p.Arg52Cys (c.154C>T) is very rare (popmax 0.00174%, amr) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EED p.Arg52Cys (c.154C>T)?

AlphaMissense predicts likely pathogenic (score 0.7548) — an in-silico prediction, not a clinical call.

EED p.Arg52Cys

c.154C>T · rs772993565 · VCV981848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.7548	likely pathogenic
REVEL	0.598	indeterminate
SaProt	LLR -7.84	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 3.9	GERP 1.3, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 5,145 bp · p 0.013 · 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 0.00174% Admixed American · 1/57,572 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000624% 10/1,601,766 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00484%	20,676
Admixed Americangrpmax	0.00174%	57,572
South Asian	0.00112%	89,290
European (non-Finnish)	0.000425%	235,036

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EED
Protein: p.Arg52Cys
Coding: c.154C>T
MANE Select: NM_003797
dbSNP: rs772993565
Type: single nucleotide variant
Location: chr11:86250335 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 52: the 'disordered' region

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

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

EED p.Asn194Ser Pathogenic/Likely pathogenic ★★ same type
EED p.Asp237Gly Likely pathogenic ★★ same type
EED p.Ala17Val Uncertain significance ★★ ⚠ same type
EED p.Arg4Met Uncertain significance ★★ ⚠ same type
EED p.Lys83Ile Uncertain significance ★★ ⚠ same type
EED c.267+20C>G Benign/Likely benign ★★ same type
EED c.268-43G>A Benign ★★ same type
EED c.361-19G>A Likely benign ★★ 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/eed-p-arg52cys (accessed [today's date]).

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