Is EDEM3 p.Ser514= (c.1542G>A) pathogenic?

EDEM3 p.Ser514= (c.1542G>A) is classified Likely benign in EDEM3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-20). Very rare (popmax 0.0027%, afr); Associated with EDEM3-related disorder.

What condition is associated with EDEM3 p.Ser514= (c.1542G>A)?

EDEM3 p.Ser514= (c.1542G>A) is associated with EDEM3-related disorder (ClinVar).

How common is EDEM3 p.Ser514= (c.1542G>A) in the general population?

EDEM3 p.Ser514= (c.1542G>A) is very rare (popmax 0.0027%, afr) (gnomAD).

EDEM3 p.Ser514=

c.1542G>A · rs770289161 · VCV3052812

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0027%, afr)

Conditions

EDEM3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP -1.8, phastCons 1
Overall
CADD	11.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0027% African / African-American · 2/74,078 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.001% 16/1,600,060 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0027%	37,039
South Asian	0.00228%	43,906
Remaining individualsnot grpmax-eligible	0.00162%	61,838
European (non-Finnish)	0.000936%	106,857

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.Ser514=
Coding: c.1542G>A
MANE Select: NM_025191
dbSNP: rs770289161
Type: single nucleotide variant
Location: chr1:184711872 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.50
Residue 514: 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

EDEM3-related disorder

Similar variants

EDEM3 p.Ser514Leu Uncertain significance ★ ⚠ same residue
EDEM3 c.345+1G>A Uncertain significance ★ same condition
EDEM3 p.Ile723Leu Uncertain significance ⚠ same condition
EDEM3 p.Arg579Lys Uncertain significance ★★ ⚠ same type
EDEM3 p.Asn691Ser Uncertain significance ★★ ⚠ same type
EDEM3 p.Asp554Val Uncertain significance ★★ ⚠ same type
EDEM3 p.His454Gln Uncertain significance ★★ ⚠ same type
EDEM3 p.Pro574Ser Uncertain significance ★★ ⚠ 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/edem3-p-ser514 (accessed [today's date]).

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