Is CASP2 p.Lys77Glu (c.229A>G) pathogenic?

CASP2 p.Lys77Glu (c.229A>G) is classified Uncertain significance in CASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.1883); Very rare (popmax 6.84e-05%).

How common is CASP2 p.Lys77Glu (c.229A>G) in the general population?

CASP2 p.Lys77Glu (c.229A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CASP2 p.Lys77Glu (c.229A>G)?

AlphaMissense predicts likely benign (score 0.1883) — an in-silico prediction, not a clinical call.

CASP2 p.Lys77Glu

c.229A>G · VCV3827544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1883	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -11.53	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 0.00043 · regional, not allelic
Overall
CADD	18.91	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,864 alleles · very 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: CASP2
Protein: p.Lys77Glu
Coding: c.229A>G
MANE Select: NM_032982
Type: single nucleotide variant
Location: chr7:143292303 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.95 · 17 PDB
Residue 77: a UniProt-annotated variant site (in mrt80; likely pathogenic); the card domain

Full CASP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP2 p.Gln331Glu Uncertain significance ★★ ⚠ same type
CASP2 p.Ala412= Likely benign ★★ same type
CASP2 p.Gly7= Likely benign ★★ same type
CASP2 p.Ile387= Benign/Likely benign ★★ same type
CASP2 p.Lys254= Benign/Likely benign ★★ same type
CASP2 p.Thr267= Benign/Likely benign ★★ same type
CASP2 p.Tyr151= Benign ★★ same type
CASP2 p.Val29= Benign ★★ 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/casp2-p-lys77glu (accessed [today's date]).

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