Is CHM p.Leu235fs (c.703dup) pathogenic?

CHM p.Leu235fs (c.703dup) is classified Pathogenic in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). Absent from gnomAD; Associated with retinitis pigmentosa.

What condition is associated with CHM p.Leu235fs (c.703dup)?

CHM p.Leu235fs (c.703dup) is associated with retinitis pigmentosa (ClinVar).

How common is CHM p.Leu235fs (c.703dup) in the general population?

CHM p.Leu235fs (c.703dup) is absent from gnomAD (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CHM p.Leu235fs

c.703dup · rs2147667670 · VCV1338868

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

retinitis pigmentosa

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 6 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.8	GERP 2.9, 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.Leu235fs
Coding: c.703dup
MANE Select: NM_000390
dbSNP: rs2147667670
Type: Duplication
Location: chrX:85958976 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Disease context

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

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CHM p.Arg253Ter Pathogenic ★★ same condition
CHM p.Met1Ile Likely pathogenic same condition
CHM p.Asn283Ter Pathogenic ★★ same type
CHM p.Asp353fs Pathogenic ★★ same type
CHM p.Glu480fs Pathogenic ★★ same type
CHM c.117-27_117-26dup Likely benign ★★ same type
CHM c.117-27dup Benign ★★ same type
CHM p.Asn644_Leu645insGlnSerThrAsn Benign/Likely benign ★★ 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/chm-p-leu235fs (accessed [today's date]).

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