Is EFR3A p.Pro218= (c.654T>G) pathogenic?

EFR3A p.Pro218= (c.654T>G) is classified Likely benign in EFR3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-14). Very rare (popmax 0.00669%, eas); Associated with EFR3A-related disorder.

What condition is associated with EFR3A p.Pro218= (c.654T>G)?

EFR3A p.Pro218= (c.654T>G) is associated with EFR3A-related disorder (ClinVar).

How common is EFR3A p.Pro218= (c.654T>G) in the general population?

EFR3A p.Pro218= (c.654T>G) is very rare (popmax 0.00669%, eas) (gnomAD).

EFR3A p.Pro218=

c.654T>G · rs760926576 · VCV3042269

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

EFR3A-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 -0.33	GERP -3.6
Overall
CADD	5.204	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,854 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000372% 6/1,612,750 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,951
European (non-Finnish)	0.000254%	393,059

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: EFR3A
Protein: p.Pro218=
Coding: c.654T>G
MANE Select: NM_015137
dbSNP: rs760926576
Type: single nucleotide variant
Location: chr8:131955783 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.11 · 1 PDB

Full EFR3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EFR3A-related disorder

Similar variants

EFR3A p.Glu725Gly Uncertain significance ★ same condition
EFR3A p.Ile215Leu Uncertain significance ★ ⚠ same condition
EFR3A c.2065+1011C>T Likely benign same condition
EFR3A c.2311-9T>A Benign same condition
EFR3A c.639-3T>C Benign same condition
EFR3A c.856-9C>T Likely benign same condition
EFR3A p.Arg214His Likely benign same condition
EFR3A p.Asn181= Benign 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/efr3a-p-pro218 (accessed [today's date]).

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