Is CHM p.Arg253Ter (c.757C>T) pathogenic?

CHM p.Arg253Ter (c.757C>T) is classified Pathogenic in CHM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-07-08). Absent from gnomAD v4.1; Associated with CHM-related disorders.

What condition is associated with CHM p.Arg253Ter (c.757C>T)?

CHM p.Arg253Ter (c.757C>T) is associated with CHM-related disorders, choroideremia, inherited retinal dystrophy (ClinVar).

How common is CHM p.Arg253Ter (c.757C>T) in the general population?

CHM p.Arg253Ter (c.757C>T) is absent from gnomAD v4.1 (gnomAD).

CHM p.Arg253Ter

c.757C>T · rs886041178 · VCV279774

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CHM-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 2.1, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHM
Protein: p.Arg253Ter
Coding: c.757C>T
MANE Select: NM_000390
dbSNP: rs886041178
Type: single nucleotide variant
Location: chrX:85958923 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Disease context

CHM-related disorders

Also linked: choroideremia inherited retinal dystrophy retinitis pigmentosa

Similar variants

CHM p.Arg253= Likely benign ★ 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.1167-2A>G Pathogenic ★★ same condition
CHM c.1244+1G>A Pathogenic ★★ same condition
CHM c.1244+2T>A Pathogenic/Likely 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-arg253ter (accessed [today's date]).

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