PHC1 p.Val615=
c.1845T>G · rs141573939 · VCV1337181
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.07%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.047 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -3.5 |
| Overall | ||
| CADD | 5.099 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.07%
African / African-American · 765/71,462 alleles
Filtering AF
1.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.983%
Overall
0.0567%
845/1,490,540 alleles · low-frequency
exomes 387/1,338,518 · genomes 458/152,022 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.07% | 93 |
| Remaining individualsnot grpmax-eligible | 0.0732% | 1,367 |
| Admixed American | 0.0728% | 1,373 |
| Middle Eastern | 0.0532% | 1,880 |
| South Asian | 0.00138% | 72,266 |
| European (non-Finnish) | 0.000269% | 372,111 |
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.Val615=
- Coding
- c.1845T>G
- MANE Select
- NM_004426
- dbSNP
- rs141573939
- Type
- single nucleotide variant
- Location
- chr12:8933302 (GRCh38)
- Gene constraint
- LOEUF 0.322 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 51.06 · 1 PDB
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-val615 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown