Is EDC3 p.Thr60= (c.180G>A) pathogenic?

EDC3 p.Thr60= (c.180G>A) is classified Likely benign in EDC3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). Ultra-rare (popmax 0.0379%, eas); Associated with EDC3-related disorder.

What condition is associated with EDC3 p.Thr60= (c.180G>A)?

EDC3 p.Thr60= (c.180G>A) is associated with EDC3-related disorder (ClinVar).

How common is EDC3 p.Thr60= (c.180G>A) in the general population?

EDC3 p.Thr60= (c.180G>A) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

EDC3 p.Thr60=

c.180G>A · rs764338631 · VCV3050496

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Conditions

EDC3-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 -2.5	GERP -3.2
Overall
CADD	8.074	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% East Asian · 17/44,886 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00285% 46/1,613,632 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,640
African / African-American	0.00267%	37,439
European (non-Finnish)	0.0022%	45,376
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: EDC3
Protein: p.Thr60=
Coding: c.180G>A
MANE Select: NM_025083
dbSNP: rs764338631
Type: single nucleotide variant
Location: chr15:74671759 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 6 PDB
Residue 60: the sm domain; a β-strand; the 'required for p-body targeting and interaction with dcp1a' region

Full EDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EDC3-related disorder

Similar variants

EDC3 p.Leu463= Likely benign same condition
EDC3 p.Ser166= Likely benign same condition
EDC3 p.Arg260Trp Uncertain significance ★★ ⚠ same type
EDC3 p.Thr273= Benign ★★ same type
EDC3 c.821-2A>C Uncertain significance ★ same type
EDC3 p.Ala129Thr Uncertain significance ★ ⚠ same type
EDC3 p.Ala172Pro Uncertain significance ★ ⚠ same type
EDC3 p.Ala312Thr 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/edc3-p-thr60 (accessed [today's date]).

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