PCLO p.Pro654=
c.1962G>A · rs377565205 · VCV1517489
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00401%, 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 -2.8 | GERP -3.4 |
| Overall | ||
| CADD | 1.205 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,734 alleles
Filtering AF
0.00107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00136%
22/1,612,964 alleles · very rare
exomes 20/1,461,268 · genomes 2/151,696 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,911 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,229 |
| Admixed American | 0.00167% | 59,894 |
| European (non-Finnish) | 0.00127% | 78,639 |
| South Asian | 0.0011% | 90,966 |
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
- PCLO
- Protein
- p.Pro654=
- Coding
- c.1962G>A
- MANE Select
- NM_033026
- dbSNP
- rs377565205
- Type
- single nucleotide variant
- Location
- chr7:83135588 (GRCh38)
- Gene constraint
- LOEUF 0.191 · pLI 1.00 (gnomAD)
- Residue 654
- the 'disordered' region
Similar variants
- PCLO p.Pro654Leu Uncertain significance ★★ ⚠ same residue
- PCLO p.Ala1410Thr Uncertain significance ★★ ⚠ same type
- PCLO p.Ala2123Val Uncertain significance ★★ ⚠ same type
- PCLO p.Ala2259Gly Uncertain significance ★★ ⚠ same type
- PCLO p.Ala3066Ser Uncertain significance ★★ ⚠ same type
- PCLO p.Ala3613Ser Uncertain significance ★★ ⚠ same type
- PCLO p.Ala3662Thr Uncertain significance ★★ ⚠ same type
- PCLO p.Ala3695Val 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/pclo-p-pro654 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown