Is CHM p.Arg555Ter (c.1663A>T) pathogenic?

CHM p.Arg555Ter (c.1663A>T) is classified Pathogenic in CHM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-14). Very rare (popmax 0.000112%, nfe); Associated with choroideremia.

What condition is associated with CHM p.Arg555Ter (c.1663A>T)?

CHM p.Arg555Ter (c.1663A>T) is associated with choroideremia (ClinVar).

How common is CHM p.Arg555Ter (c.1663A>T) in the general population?

CHM p.Arg555Ter (c.1663A>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

How is Choroideremia inherited?

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

CHM p.Arg555Ter

c.1663A>T · rs2148120604 · VCV1073117

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

choroideremia

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 14 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2, phastCons 1
Overall
CADD	36.0	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

Grpmax group 0.000112% European (non-Finnish) · 1/891,169 alleles

Overall 9.16e-05% 1/1,091,991 alleles · very rare

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.Arg555Ter
Coding: c.1663A>T
MANE Select: NM_000390
dbSNP: rs2148120604
Type: single nucleotide variant
Location: chrX:85873159 (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.Arg555Thr 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-arg555ter (accessed [today's date]).

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