Is CASP2 p.Ala19Thr (c.55G>A) pathogenic?

CASP2 p.Ala19Thr (c.55G>A) is classified Likely benign in CASP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-09-08). AlphaMissense: likely benign (0.0793); Rare (popmax 0.245%, afr); Associated with CASP2-related disorder.

What condition is associated with CASP2 p.Ala19Thr (c.55G>A)?

CASP2 p.Ala19Thr (c.55G>A) is associated with CASP2-related disorder (ClinVar).

How common is CASP2 p.Ala19Thr (c.55G>A) in the general population?

CASP2 p.Ala19Thr (c.55G>A) is rare (popmax 0.245%, afr) (gnomAD).

What do computational predictors say about CASP2 p.Ala19Thr (c.55G>A)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

CASP2 p.Ala19Thr

c.55G>A · rs145693200 · VCV3057249

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.245%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CASP2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP 2.8, phastCons 0.35
Regional constraint	o/e 1.33	unconstrained · MANE · 3,164 bp · p 0.0077 · regional, not allelic
Overall
CADD	16.53	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 0.245% African / African-American · 184/75,042 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0131% 212/1,613,346 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.245%	408
Middle Eastern	0.0862%	1,160
Remaining individualsnot grpmax-eligible	0.0208%	4,802
Admixed American	0.0117%	8,573
South Asian	0.0011%	91,056
European (non-Finnish)	0.00017%	589,814

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.Ala19Thr
Coding: c.55G>A
MANE Select: NM_032982
dbSNP: rs145693200
Type: single nucleotide variant
Location: chr7:143288510 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.95 · 17 PDB

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

Disease context

CASP2-related disorder

Similar variants

CASP2 c.876+9A>G Likely benign same condition
CASP2 p.Asn302= Likely benign same condition
CASP2 p.His337= Likely benign same condition
CASP2 p.Pro178Ala Likely benign same condition
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

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-ala19thr (accessed [today's date]).

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