Is CHM p.Thr643= (c.1929A>C) pathogenic?

CHM p.Thr643= (c.1929A>C) is classified Benign/Likely benign in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-17). Ultra-rare (popmax 0.0141%, nfe); Associated with choroideremia.

What condition is associated with CHM p.Thr643= (c.1929A>C)?

CHM p.Thr643= (c.1929A>C) is associated with choroideremia (ClinVar).

How common is CHM p.Thr643= (c.1929A>C) in the general population?

CHM p.Thr643= (c.1929A>C) is ultra-rare (popmax 0.0141%, nfe) (gnomAD).

How is Choroideremia inherited?

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

CHM p.Thr643=

c.1929A>C · rs747278560 · VCV1165534

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, nfe)

Conditions

choroideremia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.8, phastCons 0.16
Overall
CADD	5.727	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0141% European (non-Finnish) · 126/894,600 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0108% 130/1,208,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0141%	7,100
South Asian	0.00531%	18,838
Remaining individualsnot grpmax-eligible	0.0021%	47,533

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.Thr643=
Coding: c.1929A>C
MANE Select: NM_000390
dbSNP: rs747278560
Type: single nucleotide variant
Location: chrX:85864663 (GRCh38)
Structure: AlphaFold pLDDT 81.05
Residue 643: the 'disordered' region

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.Thr643Ile 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-thr643 (accessed [today's date]).

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