Is EFHC1 p.Phe438fs (c.1314del) pathogenic?

EFHC1 p.Phe438fs (c.1314del) is classified Pathogenic in EFHC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-03-03). Very rare (popmax 0.0011%, sas).

How common is EFHC1 p.Phe438fs (c.1314del) in the general population?

EFHC1 p.Phe438fs (c.1314del) is very rare (popmax 0.0011%, sas) (gnomAD).

EFHC1 p.Phe438fs

c.1314del · rs796052421 · VCV205420

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.49	GERP -3.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Overall 6.84e-05% 1/1,461,752 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.Phe438fs
Coding: c.1314del
MANE Select: NM_018100
dbSNP: rs796052421
Type: Deletion
Location: chr6:52479070 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB
Residue 438: the dm10 3 domain

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

Similar variants

EFHC1 p.Asp228fs Uncertain significance ★★ same type
EFHC1 p.Gln395fs Uncertain significance ★★ same type
EFHC1 p.Ile367fs Uncertain significance ★★ same type
EFHC1 p.Asp167fs Uncertain significance ★ same type
EFHC1 p.Asp363fs Uncertain significance ★ same type
EFHC1 p.Glu391fs Uncertain significance ★ same type
EFHC1 p.Ile122_Tyr123del Uncertain significance ★ same type
EFHC1 c.1138-293del Benign ★ 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/efhc1-p-phe438fs (accessed [today's date]).

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