Is CHM p.Asp3Gly (c.8A>G) pathogenic?

CHM p.Asp3Gly (c.8A>G) is classified Benign/Likely benign in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-21). AlphaMissense: likely benign (0.2057); Ultra-rare (popmax 0.048%, nfe); Associated with choroideremia.

What condition is associated with CHM p.Asp3Gly (c.8A>G)?

CHM p.Asp3Gly (c.8A>G) is associated with choroideremia (ClinVar).

How common is CHM p.Asp3Gly (c.8A>G) in the general population?

CHM p.Asp3Gly (c.8A>G) is ultra-rare (popmax 0.048%, nfe) (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.Asp3Gly (c.8A>G)?

AlphaMissense predicts likely benign (score 0.2057) — an in-silico prediction, not a clinical call.

CHM p.Asp3Gly

c.8A>G · rs149255670 · VCV704772

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.048%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

choroideremia

Computational evidence

Protein change
AlphaMissense	0.2057	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -0.66, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	22.7	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 0.048% European (non-Finnish) · 428/891,235 alleles

Filtering AF 0.0442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0428%

Overall 0.0382% 460/1,203,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.048%	2,082
African / African-American	0.0281%	3,563
Remaining individualsnot grpmax-eligible	0.0232%	4,308
Admixed American	0.011%	9,094

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.Asp3Gly
Coding: c.8A>G
MANE Select: NM_000390
dbSNP: rs149255670
Type: single nucleotide variant
Location: chrX:86047525 (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.Asp3Asn 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-asp3gly (accessed [today's date]).

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