Is CHM p.Ter654Gln (c.1960T>C) pathogenic?

CHM p.Ter654Gln (c.1960T>C) is classified Uncertain significance in CHM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-23). Very rare (popmax 0.0089%, eas); Associated with choroideremia.

What condition is associated with CHM p.Ter654Gln (c.1960T>C)?

CHM p.Ter654Gln (c.1960T>C) is associated with choroideremia (ClinVar).

How common is CHM p.Ter654Gln (c.1960T>C) in the general population?

CHM p.Ter654Gln (c.1960T>C) is very rare (popmax 0.0089%, eas) (gnomAD).

How is Choroideremia inherited?

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

CHM p.Ter654Gln

c.1960T>C · rs1168750683 · VCV1698965

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0089%, eas)

Conditions

choroideremia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -1.1, phastCons 1
Overall
CADD	12.61	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 0.0089% East Asian · 3/33,723 alleles

Filtering AF 0.00236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.000274% 3/1,094,050 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.Ter654Gln
Coding: c.1960T>C
MANE Select: NM_000390
dbSNP: rs1168750683
Type: single nucleotide variant
Location: chrX:85864632 (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.Ter654Glu 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-ter654gln (accessed [today's date]).

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