Is CHM p.Leu550Val (c.1648C>G) pathogenic?

CHM p.Leu550Val (c.1648C>G) is classified Uncertain significance in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0666); Very rare (popmax 0.00701%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHM p.Leu550Val (c.1648C>G)?

CHM p.Leu550Val (c.1648C>G) is associated with Inborn genetic diseases, choroideremia (ClinVar).

How common is CHM p.Leu550Val (c.1648C>G) in the general population?

CHM p.Leu550Val (c.1648C>G) is very rare (popmax 0.00701%, afr) (gnomAD).

What do computational predictors say about CHM p.Leu550Val (c.1648C>G)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

CHM p.Leu550Val

c.1648C>G · rs186479811 · VCV964541

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00701%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -3.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	17.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00701% African / African-American · 4/57,031 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.000417% 5/1,199,724 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00701%	14,258
European (non-Finnish)	0.000113%	887,981

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.Leu550Val
Coding: c.1648C>G
MANE Select: NM_000390
dbSNP: rs186479811
Type: single nucleotide variant
Location: chrX:85873174 (GRCh38)
Structure: AlphaFold pLDDT 81.05
Residue 550: a UniProt-annotated variant site (in chm)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: choroideremia

Similar variants

CHM p.Leu550Pro Likely pathogenic ★ 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-leu550val (accessed [today's date]).

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