Is CHM p.Glu194= (c.582A>G) pathogenic?

CHM p.Glu194= (c.582A>G) is classified Benign in CHM (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-04). Ultra-rare (popmax 0.0174%, amr); Associated with choroideremia.

What condition is associated with CHM p.Glu194= (c.582A>G)?

CHM p.Glu194= (c.582A>G) is associated with choroideremia (ClinVar).

How common is CHM p.Glu194= (c.582A>G) in the general population?

CHM p.Glu194= (c.582A>G) is ultra-rare (popmax 0.0174%, amr) (gnomAD).

How is Choroideremia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CHM p.Glu194=

c.582A>G · rs1444964030 · VCV787552

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, amr)

Conditions

choroideremia

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 -2.3	GERP -4.5
Overall
CADD	0.386	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% Admixed American · 8/46,070 alleles

Filtering AF 0.00864% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00627%

Overall 0.00082% 9/1,098,143 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0174%	5,759
Remaining individualsnot grpmax-eligible	0.0021%	47,651

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: CHM
Protein: p.Glu194=
Coding: c.582A>G
MANE Select: NM_000390
dbSNP: rs1444964030
Type: single nucleotide variant
Location: chrX:85963785 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Disease context

choroideremia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Choroideremia (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CHM p.Glu194Gly Uncertain significance ★ ⚠ same residue
CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.116+1G>T Pathogenic/Likely pathogenic ★★ same condition
CHM c.1166+1G>A Pathogenic ★★ same condition
CHM c.1166+1G>C Pathogenic ★★ same condition
CHM c.1350-1G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.1413+1G>T Pathogenic ★★ same condition
CHM c.1511-1G>A Pathogenic ★★ 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/chm-p-glu194 (accessed [today's date]).

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