Is CHM p.Glu99fs (c.294_295del) pathogenic?

CHM p.Glu99fs (c.294295del) is classified Pathogenic in CHM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-09-29). Absent from gnomAD; Associated with choroideremia.

What condition is associated with CHM p.Glu99fs (c.294_295del)?

CHM p.Glu99fs (c.294_295del) is associated with choroideremia (ClinVar).

How common is CHM p.Glu99fs (c.294_295del) in the general population?

CHM p.Glu99fs (c.294_295del) is absent from gnomAD (gnomAD).

How is Choroideremia inherited?

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

CHM p.Glu99fs

c.294_295del · rs2520318107 · VCV2661903

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

choroideremia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 2.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHM
Protein: p.Glu99fs
Coding: c.294_295del
MANE Select: NM_000390
dbSNP: rs2520318107
Type: Deletion
Location: chrX:85978786 (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.Asp10fs Pathogenic ★★ same condition
CHM p.Glu99Ter Pathogenic/Likely pathogenic ★★ same residue
CHM p.Pro189fs Pathogenic ★★ same condition
CHM p.Ser105Argfs Pathogenic ★★ same condition
CHM p.Ser218fs Pathogenic ★★ same condition
CHM p.Ser468fs Pathogenic/Likely pathogenic ★★ same condition
CHM p.Ser561fs Pathogenic/Likely pathogenic ★★ same condition
CHM p.Tyr321fs 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-glu99fs (accessed [today's date]).

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