CHM p.Thr496=
c.1488G>A · rs74349919 · VCV283783
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.37%, eas)
Conditions
1
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 -1.8 | GERP -3.8 |
| Overall | ||
| CADD | 5.002 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.37%
East Asian · 1,471/33,664 alleles
Filtering AF
4.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.11%
Overall
0.201%
2,426/1,206,688 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.37% | 23 |
| South Asian | 0.559% | 179 |
| Ashkenazi Jewishnot grpmax-eligible | 0.504% | 198 |
| African / African-American | 0.43% | 232 |
| Remaining individualsnot grpmax-eligible | 0.356% | 281 |
| Admixed American | 0.109% | 915 |
| Middle Eastern | 0.046% | 2,174 |
| European (non-Finnish) | 0.00672% | 14,874 |
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.Thr496=
- Coding
- c.1488G>A
- MANE Select
- NM_000390
- dbSNP
- rs74349919
- Type
- single nucleotide variant
- Location
- chrX:85894210 (GRCh38)
- Structure
- AlphaFold pLDDT 81.05
Similar variants
- 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
- CHM p.Arg267Ter 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-thr496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown