Is EED p.Ser7Leu (c.20C>T) pathogenic?

EED p.Ser7Leu (c.20C>T) is classified Benign in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). AlphaMissense: likely benign (0.107); Ultra-rare (popmax 0.0165%, mid).

How common is EED p.Ser7Leu (c.20C>T) in the general population?

EED p.Ser7Leu (c.20C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about EED p.Ser7Leu (c.20C>T)?

AlphaMissense predicts likely benign (score 0.107) — an in-silico prediction, not a clinical call.

EED p.Ser7Leu

c.20C>T · VCV3910904

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.107	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -7.61	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 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 5,145 bp · p 0.013 · regional, not allelic
Overall
CADD	22.7	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00551%

Overall 0.000806% 13/1,613,212 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
African / African-American	0.0134%	7,480
European (non-Finnish)	0.00017%	589,946

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.Ser7Leu
Coding: c.20C>T
MANE Select: NM_003797
Type: single nucleotide variant
Location: chr11:86245249 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 7: the 'disordered' region

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

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-ser7leu (accessed [today's date]).

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