Is ERMARD p.Tyr636fs (c.1907del) pathogenic?

ERMARD p.Tyr636fs (c.1907del) is classified Uncertain significance in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). Very rare (popmax 8.48e-05%, nfe); Associated with periventricular nodular heterotopia 6.

What condition is associated with ERMARD p.Tyr636fs (c.1907del)?

ERMARD p.Tyr636fs (c.1907del) is associated with periventricular nodular heterotopia 6 (ClinVar).

How common is ERMARD p.Tyr636fs (c.1907del) in the general population?

ERMARD p.Tyr636fs (c.1907del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ERMARD p.Tyr636fs

c.1907del · VCV3593394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

periventricular nodular heterotopia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (18 of 18) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.89	GERP -0.55, phastCons 0.36
Overall
CADD	13.57	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,810 alleles

Overall 0.000657% 1/152,194 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: ERMARD
Protein: p.Tyr636fs
Coding: c.1907del
MANE Select: NM_018341
Type: Deletion
Location: chr6:169781383 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.79

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

Disease context

periventricular nodular heterotopia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERMARD c.1521-82del Uncertain significance ★ same condition
ERMARD p.Arg544fs Uncertain significance ★ same condition
ERMARD p.Asp358fs Uncertain significance ★ same condition
ERMARD p.Cys495del Uncertain significance ★ same condition
ERMARD p.His476fs Uncertain significance ★ same condition
ERMARD p.Pro504fs Uncertain significance ★ same condition
ERMARD p.Tyr636= Likely benign ★ same residue
ERMARD p.Glu105Gly 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/ermard-p-tyr636fs (accessed [today's date]).

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