PHC1 p.Ala512=
c.1536C>T · rs202158376 · VCV436307
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.31%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -2, phastCons 0.003 |
| Overall | ||
| CADD | 8.898 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.31%
African / African-American · 1,654/49,932 alleles
Filtering AF
3.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.13%
Overall
0.288%
1,985/688,878 alleles · low-frequency
exomes 771/558,116 · genomes 1,214/130,762 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.31% | 30 |
| Remaining individualsnot grpmax-eligible | 0.368% | 272 |
| Middle Eastern | 0.308% | 325 |
| Admixed American | 0.262% | 382 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0559% | 1,789 |
| European (non-Finnish) | 0.0194% | 5,167 |
| South Asian | 0.00872% | 11,472 |
| Finnishnot grpmax-eligible | 0.00225% | 44,516 |
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
- PHC1
- Protein
- p.Ala512=
- Coding
- c.1536C>T
- MANE Select
- NM_004426
- dbSNP
- rs202158376
- Type
- single nucleotide variant
- Location
- chr12:8932993 (GRCh38)
- Gene constraint
- LOEUF 0.322 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 51.06 · 1 PDB
- Residue 512
- the 'disordered' region
Similar variants
- PHC1 p.Arg876Gln Uncertain significance ★★ ⚠ same type
- PHC1 p.Arg876Trp Uncertain significance ★★ ⚠ same type
- PHC1 p.Arg939His Uncertain significance ★★ ⚠ same type
- PHC1 p.Glu684Ala Uncertain significance ★★ ⚠ same type
- PHC1 p.His629Asn Uncertain significance ★★ ⚠ same type
- PHC1 c.1106-60G>A Benign ★★ same type
- PHC1 c.114+191T>C Benign ★★ same type
- PHC1 c.1894-221A>G Benign ★★ 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/phc1-p-ala512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown