Is EFHC1 p.Val512= (c.1536T>G) pathogenic?

EFHC1 p.Val512= (c.1536T>G) is classified Likely benign in EFHC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-07). Very rare (popmax 0.00169%, nfe); Associated with Absence seizure.

What condition is associated with EFHC1 p.Val512= (c.1536T>G)?

EFHC1 p.Val512= (c.1536T>G) is associated with Absence seizure, myoclonic epilepsy, juvenile, susceptibility to, 1 (ClinVar).

How common is EFHC1 p.Val512= (c.1536T>G) in the general population?

EFHC1 p.Val512= (c.1536T>G) is very rare (popmax 0.00169%, nfe) (gnomAD).

EFHC1 p.Val512=

c.1536T>G · rs775581363 · VCV1108176

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Conditions

Absence seizure

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 -0.078	GERP -4.5, phastCons 0.001
Overall
CADD	8.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,044 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00124% 20/1,614,078 alleles · very rare

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.Val512=
Coding: c.1536T>G
MANE Select: NM_018100
dbSNP: rs775581363
Type: single nucleotide variant
Location: chr6:52479683 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB
Residue 512: the dm10 3 domain

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

Disease context

Absence seizure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myoclonic epilepsy, juvenile, susceptibility to, 1

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-val512 (accessed [today's date]).

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