Is ERMARD p.Pro504fs (c.1511del) pathogenic?

ERMARD p.Pro504fs (c.1511del) is classified Uncertain significance in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-14). Very rare (popmax 0.0011%, sas); Associated with periventricular nodular heterotopia 6.

What condition is associated with ERMARD p.Pro504fs (c.1511del)?

ERMARD p.Pro504fs (c.1511del) is associated with periventricular nodular heterotopia 6 (ClinVar).

How common is ERMARD p.Pro504fs (c.1511del) in the general population?

ERMARD p.Pro504fs (c.1511del) is very rare (popmax 0.0011%, sas) (gnomAD).

ERMARD p.Pro504fs

c.1511del · rs1328981245 · VCV1299254

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 0.0011%, sas)

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	predicted	premature termination codon in exon 15 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.7
Overall
CADD	21.3	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 0.0011% South Asian · 1/90,892 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,856 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,892
European (non-Finnish)	0.000339%	294,984

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.Pro504fs
Coding: c.1511del
MANE Select: NM_018341
dbSNP: rs1328981245
Type: Deletion
Location: chr6:169776055 (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.Tyr636fs Uncertain significance ★ same condition
ERMARD p.Glu105Gly Uncertain significance ★★ ⚠ same condition
ERMARD p.Thr211Met 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-pro504fs (accessed [today's date]).

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