Is CHM p.His507Arg (c.1520A>G) pathogenic?

CHM p.His507Arg (c.1520A>G) is classified Pathogenic/Likely pathogenic in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-20). AlphaMissense: likely pathogenic (0.9442); Very rare (popmax 9.37e-05%); Associated with choroideremia.

What condition is associated with CHM p.His507Arg (c.1520A>G)?

CHM p.His507Arg (c.1520A>G) is associated with choroideremia (ClinVar).

How common is CHM p.His507Arg (c.1520A>G) in the general population?

CHM p.His507Arg (c.1520A>G) is very rare (popmax 9.37e-05%) (gnomAD).

How is Choroideremia inherited?

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

What do computational predictors say about CHM p.His507Arg (c.1520A>G)?

AlphaMissense predicts likely pathogenic (score 0.9442) — an in-silico prediction, not a clinical call.

CHM p.His507Arg

c.1520A>G · rs397514603 · VCV39809

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9442 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.37e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

choroideremia

Computational evidence

Protein change
AlphaMissense	0.9442	likely pathogenic ✓ concordant with ClinVar · top 9% in CHM
REVEL	0.747	pathogenic-leaning
SaProt	LLR -13.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.62, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.37e-05%

Overall 9.37e-05% 1/1,067,739 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.His507Arg
Coding: c.1520A>G
MANE Select: NM_000390
dbSNP: rs397514603
Type: single nucleotide variant
Location: chrX:85879054 (GRCh38)
Structure: AlphaFold pLDDT 81.05
Residue 507: a UniProt-annotated variant site (in chm; impairs the interaction with rabggta)

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.His507= 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.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-his507arg (accessed [today's date]).

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