ALCAM p.Thr301=
c.903G>A · VCV4639880
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, 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 4.1 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 12.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,842 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00905%
Overall
0.00143%
23/1,612,132 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,346 |
| East Asian | 0.00446% | 22,404 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,198 |
| Admixed American | 0.00167% | 59,820 |
| South Asian | 0.0011% | 91,010 |
| European (non-Finnish) | 0.000254% | 392,930 |
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
- ALCAM
- Protein
- p.Thr301=
- Coding
- c.903G>A
- MANE Select
- NM_001627
- Type
- single nucleotide variant
- Location
- chr3:105541677 (GRCh38)
- Gene constraint
- LOEUF 0.474 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.13 · 1 PDB
- Residue 301
- a disulfide bond; a UniProt-annotated variant site (in); the ig-like c2-type 1 domain
Similar variants
- ALCAM p.Thr301Met Benign ★★ ⚠ same residue
- ALCAM p.Asp81= Benign ★★ same type
- ALCAM p.His508= Benign/Likely benign ★★ same type
- ALCAM p.Leu254= Benign ★★ same type
- ALCAM p.Pro84Leu Benign ★★ ⚠ same type
- ALCAM p.Ser454= Benign/Likely benign ★★ same type
- ALCAM p.Tyr224= Benign ★★ same type
- ALCAM p.Ala19Pro 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/alcam-p-thr301 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown