PROC c.237+301G>A
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 35.4%, sas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +301 | deep intronic (+301 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.3 | |
| Overall | ||
| CADD | 0.091 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
35.4%
South Asian · 1,706/4,820 alleles
Filtering AF
34%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 33.4%
Overall
21.1%
32,088/152,040 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 35.4% | 3 |
| Finnishnot grpmax-eligible | 26.1% | 4 |
| East Asian | 25.9% | 4 |
| European (non-Finnish) | 22.4% | 4 |
| Remaining individualsnot grpmax-eligible | 22.2% | 5 |
| Middle Eastern | 18% | 6 |
| Admixed American | 17.6% | 6 |
| African / African-American | 17.5% | 6 |
| Ashkenazi Jewishnot grpmax-eligible | 15.7% | 6 |
| Amishnot grpmax-eligible | 8.13% | 12 |
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
- PROC
- Coding
- c.237+301G>A
- MANE Select
- NM_000312
- dbSNP
- rs2069918
- Type
- single nucleotide variant
- Location
- chr2:127421750 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.35 · 12 PDB
Similar variants
- PROC p.Ala178Pro Likely pathogenic ★★ ⚠ same type
- PROC p.Ala309Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg199Ter Pathogenic ★★ same type
- PROC p.Arg211Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg211Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg220Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg220Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg271Trp Pathogenic/Likely pathogenic ★★ 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/proc-c-237-plus-301g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown