Is ERMARD p.Asp338= (c.1014T>C) pathogenic?

ERMARD p.Asp338= (c.1014T>C) is classified Benign/Likely benign in ERMARD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-13). Low-frequency (popmax 4.02%, afr); Associated with periventricular nodular heterotopia 6.

What condition is associated with ERMARD p.Asp338= (c.1014T>C)?

ERMARD p.Asp338= (c.1014T>C) is associated with periventricular nodular heterotopia 6 (ClinVar).

How common is ERMARD p.Asp338= (c.1014T>C) in the general population?

ERMARD p.Asp338= (c.1014T>C) is low-frequency (popmax 4.02%, afr) (gnomAD).

ERMARD p.Asp338=

c.1014T>C · rs61747671 · VCV384622

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.02%, afr)

Conditions

periventricular nodular heterotopia 6

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 -1.1	GERP -3.4, phastCons 0.004
Overall
CADD	7.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.02% African / African-American · 3,016/75,044 alleles

Filtering AF 3.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.85%

Overall 0.215% 3,470/1,614,094 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.02%	25
Remaining individualsnot grpmax-eligible	0.315%	317
Admixed American	0.267%	375
Middle Eastern	0.231%	433
South Asian	0.0165%	6,072
European (non-Finnish)	0.00576%	17,352

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.Asp338=
Coding: c.1014T>C
MANE Select: NM_018341
dbSNP: rs61747671
Type: single nucleotide variant
Location: chr6:169768126 (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.Asp338Gly Uncertain significance ★ ⚠ 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 c.605+1G>A Likely pathogenic ★ same condition
ERMARD p.Arg93Ter 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-asp338 (accessed [today's date]).

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