TGM1 p.Arg656=
c.1966C>A · rs144318024 · VCV1136712
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0733%, afr)
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 1.2 | GERP -3.7, phastCons 0.77 |
| Overall | ||
| CADD | 6.157 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0733%
African / African-American · 55/75,050 alleles
Filtering AF
0.0578%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0522%
Overall
0.00378%
61/1,613,960 alleles · ultra-rare
exomes 27/1,461,632 · genomes 34/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0733% | 1,365 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| Admixed American | 0.00333% | 30,013 |
| South Asian | 0.0011% | 91,084 |
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
- TGM1
- Protein
- p.Arg656=
- Coding
- c.1966C>A
- MANE Select
- NM_000359
- dbSNP
- rs144318024
- Type
- single nucleotide variant
- Location
- chr14:24254786 (GRCh38)
- Gene constraint
- LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.04 · 1 PDB
Similar variants
- TGM1 p.Arg656Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- TGM1 p.Arg656Trp Uncertain significance ★ ⚠ same residue
- TGM1 c.1159+1G>T Pathogenic ★★ same type
- TGM1 c.1645+1G>T Pathogenic/Likely pathogenic ★★ same type
- TGM1 c.2226-2A>G Pathogenic/Likely pathogenic ★★ same type
- TGM1 c.319+2T>C Likely pathogenic ★★ same type
- TGM1 c.876+2T>C Pathogenic/Likely pathogenic ★★ same type
- TGM1 c.877-2A>G Pathogenic ★★ same type
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/tgm1-p-arg656 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown