Is EDEM3 p.Thr513Ser (c.1538C>G) pathogenic?

EDEM3 p.Thr513Ser (c.1538C>G) is classified Uncertain significance in EDEM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0758); Very rare (popmax 0.00793%, amr); Associated with Inborn genetic diseases.

What condition is associated with EDEM3 p.Thr513Ser (c.1538C>G)?

EDEM3 p.Thr513Ser (c.1538C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EDEM3 p.Thr513Ser (c.1538C>G) in the general population?

EDEM3 p.Thr513Ser (c.1538C>G) is very rare (popmax 0.00793%, amr) (gnomAD).

What do computational predictors say about EDEM3 p.Thr513Ser (c.1538C>G)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

EDEM3 p.Thr513Ser

c.1538C>G · VCV3506671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00793%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.49	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 8.7	GERP 2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 2,044 bp · p 0.22 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00793% Admixed American · 4/50,428 alleles

Filtering AF 0.00265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00155%

Overall 0.000317% 5/1,577,342 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00793%	12,607
European (non-Finnish)	8.56e-05%	1,167,958

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: EDEM3
Protein: p.Thr513Ser
Coding: c.1538C>G
MANE Select: NM_025191
Type: single nucleotide variant
Location: chr1:184711876 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.50
Residue 513: a UniProt-annotated variant site (in cdg2v; uncertain significance)

Full EDEM3 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

EDEM3 p.Arg579Lys Uncertain significance ★★ ⚠ same condition
EDEM3 p.Asn691Ser Uncertain significance ★★ ⚠ same condition
EDEM3 p.His454Gln Uncertain significance ★★ ⚠ same condition
EDEM3 p.Pro574Ser Uncertain significance ★★ ⚠ same condition
EDEM3 p.Ala17Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
EDEM3 p.Ala245Thr Uncertain significance ★ ⚠ same condition
EDEM3 p.Ala41Val Uncertain significance ★ ⚠ same condition
EDEM3 p.Ala437Ser 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/edem3-p-thr513ser (accessed [today's date]).

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