Is CASP12 c.766A>C pathogenic?

CASP12 c.766A>C is classified Uncertain significance in CASP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-06). Very rare (popmax 0.00196%, amr).

How common is CASP12 c.766A>C in the general population?

CASP12 c.766A>C is very rare (popmax 0.00196%, amr) (gnomAD).

CASP12 c.766A>C

VCV3263419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.075	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -3.9
Non-coding constraint	Z 0.92	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	0.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00196% Admixed American · 1/50,930 alleles

Overall 0.000196% 3/1,534,510 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00334%	29,962
Admixed Americangrpmax	0.00196%	50,930

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.766A>C
Type: single nucleotide variant
Location: chr11:104890425 (GRCh38)
Structure: AlphaFold pLDDT 77.13

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-c-766a-c (accessed [today's date]).

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