P4HB p.Pro313=
c.939G>A · rs200780339 · VCV2896810
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0423%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.051 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -5.2 |
| Overall | ||
| CADD | 0.803 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0423%
East Asian · 19/44,878 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.023%
Overall
0.00341%
55/1,614,022 alleles · ultra-rare
exomes 53/1,461,802 · genomes 2/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0423% | 2,362 |
| European (non-Finnish) | 0.0028% | 35,758 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| African / African-American | 0.00133% | 75,018 |
| South Asian | 0.0011% | 91,080 |
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
- P4HB
- Protein
- p.Pro313=
- Coding
- c.939G>A
- MANE Select
- NM_000918
- dbSNP
- rs200780339
- Type
- single nucleotide variant
- Location
- chr17:81846546 (GRCh38)
- Gene constraint
- LOEUF 0.561 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 88.62 · 14 PDB
- Residue 313
- a β-strand
Similar variants
- P4HB p.Cys400Arg Likely pathogenic ★★ same type
- P4HB p.Arg452Lys Uncertain significance ★★ ⚠ same type
- P4HB p.Arg78Thr Uncertain significance ★★ same type
- P4HB p.Asn189Ser Uncertain significance ★★ ⚠ same type
- P4HB p.Asp365Glu Uncertain significance ★★ ⚠ same type
- P4HB p.Cys400Tyr Uncertain significance ★★ ⚠ same type
- P4HB p.Gln475Arg Uncertain significance ★★ ⚠ same type
- P4HB p.Glu121Gly 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/p4hb-p-pro313 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown