Is EFHC1 p.Asn35= (c.105C>T) pathogenic?

EFHC1 p.Asn35= (c.105C>T) is classified Likely benign in EFHC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-07). Ultra-rare (popmax 0.033%, mid); Associated with Absence seizure.

What condition is associated with EFHC1 p.Asn35= (c.105C>T)?

EFHC1 p.Asn35= (c.105C>T) is associated with Absence seizure, myoclonic epilepsy, juvenile, susceptibility to, 1 (ClinVar).

How common is EFHC1 p.Asn35= (c.105C>T) in the general population?

EFHC1 p.Asn35= (c.105C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

EFHC1 p.Asn35=

c.105C>T · rs534406651 · VCV1137266

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -5.8	GERP -3.5
Overall
CADD	3.397	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00335% 54/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0209%	4,793
Remaining individualsnot grpmax-eligible	0.0064%	15,626
East Asian	0.00446%	22,443
European (non-Finnish)	0.00229%	43,704

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.Asn35=
Coding: c.105C>T
MANE Select: NM_018100
dbSNP: rs534406651
Type: single nucleotide variant
Location: chr6:52423987 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB
Residue 35: the 'required for its localization in the mitotic spindle and interaction with alpha-tubulin' region

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.Asn35Ser Uncertain significance ★ ⚠ same residue
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

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-asn35 (accessed [today's date]).

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