Is EFHC1 p.Pro543= (c.1629A>G) pathogenic?

EFHC1 p.Pro543= (c.1629A>G) is classified Likely benign in EFHC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-23). Very rare (popmax 0.005%, amr); Associated with myoclonic epilepsy, juvenile, susceptibility to, 1.

What condition is associated with EFHC1 p.Pro543= (c.1629A>G)?

EFHC1 p.Pro543= (c.1629A>G) is associated with myoclonic epilepsy, juvenile, susceptibility to, 1 (ClinVar).

How common is EFHC1 p.Pro543= (c.1629A>G) in the general population?

EFHC1 p.Pro543= (c.1629A>G) is very rare (popmax 0.005%, amr) (gnomAD).

EFHC1 p.Pro543=

c.1629A>G · rs1422352360 · VCV1158336

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

myoclonic epilepsy, juvenile, susceptibility to, 1

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 0.14	GERP -4.2, phastCons 0.001
Overall
CADD	3.657	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,032 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000342% 5/1,461,792 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,011
African / African-American	0.00133%	75,054
European (non-Finnish)	8.47e-05%	1,180,026

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: EFHC1
Protein: p.Pro543=
Coding: c.1629A>G
MANE Select: NM_018100
dbSNP: rs1422352360
Type: single nucleotide variant
Location: chr6:52479776 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB
Residue 543: the 'disordered' region

Full EFHC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myoclonic epilepsy, juvenile, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFHC1 p.Ala445Thr Uncertain significance ★★ ⚠ same condition
EFHC1 p.Ala529Glu Uncertain significance ★★ ⚠ same condition
EFHC1 p.Ala590Pro Uncertain significance ★★ ⚠ same condition
EFHC1 p.Ala83Val Uncertain significance ★★ ⚠ same condition
EFHC1 p.Ala88Val Uncertain significance ★★ ⚠ same condition
EFHC1 p.Arg118Cys Uncertain significance ★★ ⚠ same condition
EFHC1 p.Arg151Leu Uncertain significance ★★ ⚠ same condition
EFHC1 p.Arg159Gln 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/efhc1-p-pro543 (accessed [today's date]).

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