Is ERMARD p.Arg93Ter (c.277C>T) pathogenic?

ERMARD p.Arg93Ter (c.277C>T) is classified Likely pathogenic in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-30). Very rare (popmax 0.00549%, sas); Associated with periventricular nodular heterotopia 6.

What condition is associated with ERMARD p.Arg93Ter (c.277C>T)?

ERMARD p.Arg93Ter (c.277C>T) is associated with periventricular nodular heterotopia 6 (ClinVar).

How common is ERMARD p.Arg93Ter (c.277C>T) in the general population?

ERMARD p.Arg93Ter (c.277C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

ERMARD p.Arg93Ter

c.277C>T · rs762266071 · VCV2429374

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

periventricular nodular heterotopia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.28	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.8	GERP 3.1, phastCons 0.032
Overall
CADD	33.0	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 0.00549% South Asian · 5/91,078 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000616% 9/1,461,870 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
European (non-Finnish)	0.000339%	295,004

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.Arg93Ter
Coding: c.277C>T
MANE Select: NM_018341
dbSNP: rs762266071
Type: single nucleotide variant
Location: chr6:169755384 (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 p.Arg93Gln Likely benign ★ same residue
ERMARD p.Glu105Gly Uncertain significance ★★ ⚠ same condition
ERMARD p.Thr211Met Uncertain significance ★★ ⚠ same condition
ERMARD c.1060-12A>G Benign/Likely benign ★★ same condition
ERMARD p.Arg502His Benign ★★ same condition
ERMARD p.Asp338= Benign/Likely benign ★★ same condition
ERMARD c.605+1G>A Likely pathogenic ★ same condition
ERMARD c.1394+1G>T 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-arg93ter (accessed [today's date]).

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