Is EDC3 p.Ala211= (c.633T>G) pathogenic?

EDC3 p.Ala211= (c.633T>G) is classified Likely benign in EDC3 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-31). Ultra-rare (popmax 0.0114%, nfe).

How common is EDC3 p.Ala211= (c.633T>G) in the general population?

EDC3 p.Ala211= (c.633T>G) is ultra-rare (popmax 0.0114%, nfe) (gnomAD).

EDC3 p.Ala211=

c.633T>G · rs138195822 · VCV754638

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, nfe)

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 1.1	GERP -3.9, phastCons 1
Overall
CADD	8.689	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0114% European (non-Finnish) · 135/1,180,030 alleles

Filtering AF 0.00986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0092%

Overall 0.0457% 737/1,614,132 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.75%	57
Remaining individualsnot grpmax-eligible	0.128%	781
European (non-Finnish)grpmax	0.0114%	8,741
Admixed American	0.005%	20,005
African / African-American	0.00133%	75,012

Ashkenazi Jewish 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: EDC3
Protein: p.Ala211=
Coding: c.633T>G
MANE Select: NM_025083
dbSNP: rs138195822
Type: single nucleotide variant
Location: chr15:74655920 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 6 PDB
Residue 211: the dfdf domain; the 'required for interaction with ddx6' region

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

Similar variants

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
EDC3 p.Arg232His Uncertain significance ★ ⚠ same type
EDC3 p.Arg243Gln 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-ala211 (accessed [today's date]).

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