Is ERMARD p.Arg367His (c.1100G>A) pathogenic?

ERMARD p.Arg367His (c.1100G>A) is classified Uncertain significance in ERMARD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.5115); Ultra-rare (popmax 0.0575%, afr).

How common is ERMARD p.Arg367His (c.1100G>A) in the general population?

ERMARD p.Arg367His (c.1100G>A) is ultra-rare (popmax 0.0575%, afr) (gnomAD).

What do computational predictors say about ERMARD p.Arg367His (c.1100G>A)?

AlphaMissense predicts ambiguous (score 0.5115) — an in-silico prediction, not a clinical call.

ERMARD p.Arg367His

c.1100G>A · rs367621676 · VCV1330218

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5115 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0575%, afr)

Computational evidence

Protein change
AlphaMissense	0.5115	ambiguous
REVEL	0.459	indeterminate
SaProt	LLR -12.90	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0575% African / African-American · 43/74,836 alleles

Filtering AF 0.0438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0391%

Overall 0.0041% 66/1,611,326 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0575%	1,740
East Asian	0.0178%	5,605
Remaining individualsnot grpmax-eligible	0.00641%	15,598
Admixed American	0.00504%	19,845
South Asian	0.00443%	22,569
European (non-Finnish)	0.000339%	294,738

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.Arg367His
Coding: c.1100G>A
MANE Select: NM_018341
dbSNP: rs367621676
Type: single nucleotide variant
Location: chr6:169769580 (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

Similar variants

ERMARD p.Arg367Cys Uncertain significance ★ same residue
ERMARD p.Ala474Val Uncertain significance ★★ ⚠ same type
ERMARD p.Arg400Ser Uncertain significance ★★ ⚠ same type
ERMARD p.Arg537Gln Uncertain significance ★★ ⚠ same type
ERMARD p.Arg544Cys Uncertain significance ★★ ⚠ same type
ERMARD p.Arg569Cys Uncertain significance ★★ ⚠ same type
ERMARD p.Arg571Gln Uncertain significance ★★ ⚠ same type
ERMARD p.Arg571Trp Uncertain significance ★★ ⚠ same type

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-arg367his (accessed [today's date]).

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