Is EMID1 p.Pro243Arg (c.728C>G) pathogenic?

EMID1 p.Pro243Arg (c.728C>G) is classified Uncertain significance in EMID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). Very rare (popmax 0.0022%, nfe).

How common is EMID1 p.Pro243Arg (c.728C>G) in the general population?

EMID1 p.Pro243Arg (c.728C>G) is very rare (popmax 0.0022%, nfe) (gnomAD).

EMID1 p.Pro243Arg

c.728C>G · rs756180356 · VCV2488631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.669	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.89, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 53 kb · p 0.62 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% European (non-Finnish) · 26/1,179,628 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00174% 28/1,611,018 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,370
Remaining individualsnot grpmax-eligible	0.0016%	62,308
African / African-American	0.00134%	74,866

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: EMID1
Protein: p.Pro243Arg
Coding: c.728C>G
MANE Select: NM_133455
dbSNP: rs756180356
Type: single nucleotide variant
Location: chr22:29232307 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77
Residue 243: the collagen-like domain; the 'disordered' region

Full EMID1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMID1 c.587-5C>G Benign ★★ same type
EMID1 p.Ala108Thr Uncertain significance ★ same type
EMID1 p.Ala112Thr Uncertain significance ★ same type
EMID1 p.Ala127Ser Uncertain significance ★ same type
EMID1 p.Ala28Thr Uncertain significance ★ same type
EMID1 p.Ala409Val Uncertain significance ★ same type
EMID1 p.Ala435Asp Uncertain significance ★ same type
EMID1 p.Ala6Ser 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/emid1-p-pro243arg (accessed [today's date]).

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