Is ERMAP p.Arg73= (c.219C>T) pathogenic?

ERMAP p.Arg73= (c.219C>T) is classified Benign in ERMAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-25). Common (popmax 8.74%, afr) — too common for a highly-penetrant pathogenic allele.

ERMAP p.Arg73=

Q: How common is ERMAP p.Arg73= (c.219C>T) in the general population?

ERMAP p.Arg73= (c.219C>T) is common (popmax 8.74%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.219C>T · rs33954154 · VCV785937

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.74%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.15	GERP 1.8
Overall
CADD	3.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.74% African / African-American · 6,554/75,006 alleles

Filtering AF 8.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.49%

Overall 0.469% 7,564/1,614,038 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.74%	11
Admixed American	0.673%	149
Remaining individualsnot grpmax-eligible	0.555%	180
Middle Eastern	0.313%	319
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
European (non-Finnish)	0.0182%	5,488
South Asian	0.0176%	5,692
Finnishnot grpmax-eligible	0.00156%	64,030

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: ERMAP
Protein: p.Arg73=
Coding: c.219C>T
MANE Select: NM_001017922
dbSNP: rs33954154
Type: single nucleotide variant
Location: chr1:42830901 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 73: the ig-like v-type domain; a disulfide bond

Full ERMAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERMAP p.Arg73His Uncertain significance ★ ⚠ same residue
ERMAP p.Arg73Leu Uncertain significance ★ ⚠ same residue
ERMAP p.Arg73Cys Benign same residue
ERMAP p.Ala4Val Benign ★★ same type
ERMAP p.Ala157Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala34Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala449Ser Uncertain significance ★ ⚠ same type
ERMAP p.Arg117His 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/ermap-p-arg73 (accessed [today's date]).

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