TIAM1 p.Asn537=
c.1611C>T · rs146784461 · VCV3039933
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.522%, 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 4.4 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 7.502 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.522%
African / African-American · 392/75,052 alleles
Filtering AF
0.48%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.463%
Overall
0.0372%
600/1,614,140 alleles · rare
exomes 352/1,461,840 · genomes 248/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.522% | 191 |
| Middle Eastern | 0.149% | 673 |
| Admixed American | 0.075% | 1,334 |
| Remaining individualsnot grpmax-eligible | 0.056% | 1,786 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0338% | 2,960 |
| European (non-Finnish) | 0.00924% | 10,826 |
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
- TIAM1
- Protein
- p.Asn537=
- Coding
- c.1611C>T
- MANE Select
- NM_001353694
- dbSNP
- rs146784461
- Type
- single nucleotide variant
- Location
- chr21:31225924 (GRCh38)
- Gene constraint
- LOEUF 0.469 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 59.82 · 10 PDB
- Residue 537
- the ph 1 domain; an α-helix
Similar variants
- TIAM1 p.Ala1004Thr Uncertain significance ★★ ⚠ same type
- TIAM1 p.Ala549Val Uncertain significance ★★ ⚠ same type
- TIAM1 p.Arg678His Uncertain significance ★★ ⚠ same type
- TIAM1 p.Glu144Lys Uncertain significance ★★ ⚠ same type
- TIAM1 p.Glu1567Asp Uncertain significance ★★ ⚠ same type
- TIAM1 p.His1010Pro Uncertain significance ★★ ⚠ same type
- TIAM1 p.Leu232Ser Uncertain significance ★★ ⚠ same type
- TIAM1 p.Lys886Arg Uncertain significance ★★ ⚠ 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/tiam1-p-asn537 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown