Is ERMARD p.Thr211Met (c.632C>T) pathogenic?

ERMARD p.Thr211Met (c.632C>T) is classified Uncertain significance in ERMARD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1077); Very rare (popmax 0.004%, afr); Associated with periventricular nodular heterotopia 6.

What condition is associated with ERMARD p.Thr211Met (c.632C>T)?

ERMARD p.Thr211Met (c.632C>T) is associated with periventricular nodular heterotopia 6 (ClinVar).

How common is ERMARD p.Thr211Met (c.632C>T) in the general population?

ERMARD p.Thr211Met (c.632C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ERMARD p.Thr211Met (c.632C>T)?

AlphaMissense predicts likely benign (score 0.1077) — an in-silico prediction, not a clinical call.

ERMARD p.Thr211Met

c.632C>T · rs770631548 · VCV1341867

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

periventricular nodular heterotopia 6

Computational evidence

Protein change
AlphaMissense	0.1077	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	GERP 2.2, phastCons 0.3
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,910 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000682% 11/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,970
South Asian	0.0022%	45,544
Finnishnot grpmax-eligible	0.00156%	64,022
European (non-Finnish)	0.000424%	236,003

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.Thr211Met
Coding: c.632C>T
MANE Select: NM_018341
dbSNP: rs770631548
Type: single nucleotide variant
Location: chr6:169759864 (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.Glu105Gly 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 p.Arg93Ter Likely pathogenic ★ same condition
ERMARD c.1394+1G>T Uncertain significance ★ same condition
ERMARD c.1395-1G>T Conflicting classifications of pathogenicity ★ 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-thr211met (accessed [today's date]).

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