Is CHM p.Thr466= (c.1398A>G) pathogenic?

CHM p.Thr466= (c.1398A>G) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with CHM p.Thr466= (c.1398A>G)?

CHM p.Thr466= (c.1398A>G) is associated with inherited retinal dystrophy (ClinVar).

How common is CHM p.Thr466= (c.1398A>G) in the general population?

CHM p.Thr466= (c.1398A>G) is absent from gnomAD v4.1 (gnomAD).

CHM p.Thr466=

c.1398A>G · rs2520095468 · VCV3028616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

inherited retinal dystrophy

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 -0.23	GERP -1.9, phastCons 0.51
Overall
CADD	7.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHM
Protein: p.Thr466=
Coding: c.1398A>G
MANE Select: NM_000390
dbSNP: rs2520095468
Type: single nucleotide variant
Location: chrX:85900661 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHM p.Thr466Ala Uncertain significance ★★ ⚠ same residue
CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.1244+1G>A Pathogenic ★★ same condition
CHM c.189+1G>A Pathogenic ★★ same condition
CHM c.49+5G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.940+1G>A Pathogenic ★★ same condition
CHM p.Arg239Ter Pathogenic ★★ same condition
CHM p.Arg253Ter 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-thr466 (accessed [today's date]).

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