PCARE p.Ala978=
c.2934C>T · rs1302465109 · VCV1969890
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, 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 3.3 | GERP 0.25, phastCons 0.9 |
| Overall | ||
| CADD | 5.034 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/75,056 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000494%
Overall
0.000248%
4/1,613,574 alleles · very rare
exomes 4/1,461,244 · genomes 0/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 25,019 |
| Admixed American | 0.00167% | 60,028 |
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
- PCARE
- Protein
- p.Ala978=
- Coding
- c.2934C>T
- MANE Select
- NM_001029883
- dbSNP
- rs1302465109
- Type
- single nucleotide variant
- Location
- chr2:29071328 (GRCh38)
- Gene constraint
- LOEUF 1.032 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 44.15 · 1 PDB
- Residue 978
- the 'disordered' region
Similar variants
- PCARE c.3668+2T>C Likely pathogenic ★★ same type
- PCARE p.Arg1202Ter Pathogenic/Likely pathogenic ★★ same type
- PCARE p.Arg425Ter Pathogenic ★★ same type
- PCARE p.Arg613Ter Pathogenic ★★ same type
- PCARE p.Arg984Ter Pathogenic ★★ same type
- PCARE p.Gln1097Ter Pathogenic/Likely pathogenic ★★ same type
- PCARE p.Gln268Ter Pathogenic ★★ same type
- PCARE p.Gln610Ter 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/pcare-p-ala978 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown