Is CASP12 p.Leu58Pro (c.173T>C) pathogenic?

CASP12 p.Leu58Pro (c.173T>C) is classified Uncertain significance in CASP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). Ultra-rare (popmax 0.0294%, amr).

How common is CASP12 p.Leu58Pro (c.173T>C) in the general population?

CASP12 p.Leu58Pro (c.173T>C) is ultra-rare (popmax 0.0294%, amr) (gnomAD).

CASP12 p.Leu58Pro

c.173T>C · rs887794828 · VCV3137572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.31	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 1.4, phastCons 0.95
Overall
CADD	17.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0294% Admixed American · 15/50,948 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.000977% 15/1,535,672 alleles · ultra-rare

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: CASP12
Protein: p.Leu58Pro
Coding: c.173T>C
dbSNP: rs887794828
Type: single nucleotide variant
Location: chr11:104897303 (GRCh38)
Structure: AlphaFold pLDDT 77.13
Residue 58: the card domain

Full CASP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP12 p.Arg125Ter Likely benign ★★ same type
CASP12 c.1013T>G Uncertain significance ★ same type
CASP12 c.107T>C Uncertain significance ★ same type
CASP12 c.19T>A Uncertain significance ★ same type
CASP12 c.22A>G Uncertain significance ★ same type
CASP12 c.254G>A Uncertain significance ★ same type
CASP12 c.269G>C Uncertain significance ★ same type
CASP12 c.274G>A 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/casp12-p-leu58pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown